Re: scelorsing colangitis/primary versus secondary

[Guest guest]

Hi ;

I'm very sorry to hear about your husband's hospitalization, and I

hope that he can get quick treatment for his Crohn's flare and

abscess.

The difference between primary sclerosing cholangitis and secondary

sclerosing cholangitis is explained in this article (below).

Basically, secondary sclerosing cholangitis has a known pathological

process, whereas primary sclerosing cholangitis does not. Examples of

secondary sclerosing cholangitis include various primary immune

deficiencies such as hyper-IgM syndrome, immune deficiency caused by

AIDS, sclerosing cholangitis caused by chemotherapy or blunt trauma

to the liver. I believe that there also a form of sclerosing

cholangitis associated with burn injury. If the doctor does not know

the cause, I suppose it may be tempting to just write " sclerosing

cholangitis " . But since PSC is often associated with inflammatory

bowel disease, and your husband has Crohn's disease, I think you

could assume that it is primary sclerosing cholangitis.

________________________________

Hepatology 44: 1063-1074 (2006)

Sclerosing cholangitis: a focus on secondary causes.

Abdalian R, Heathcote EJ

Department of Medicine, University Health Network, Toronto Western

Hospital, University of Toronto, Toronto, Ontario, Canada.

Secondary sclerosing cholangitis (SSC) is a disease that is

morphologically similar to primary sclerosing cholangitis (PSC) but

that originates from a known pathological process. Its clinical and

cholangiographic features may mimic PSC, yet its natural history may

be more favorable if recognition is prompt and appropriate therapy is

introduced. Thus, the diagnosis of PSC requires the exclusion of

secondary causes of sclerosing cholangitis and recognition of

associated conditions that may potentially imitate its classic

cholangiographic features. Well-described causes of SSC include

intraductal stone disease, surgical or blunt abdominal trauma, intra-

arterial chemotherapy, and recurrent pancreatitis. However, a wide

variety of other associations have been reported recently, including

autoimmune pancreatitis, portal biliopathy, eosinophillic and/or mast

cell cholangitis, hepatic inflammatory pseudotumor, recurrent

pyogenic cholangitis, primary immune deficiency, and AIDS-related

cholangiopathy. This article offers a comprehensive review of SSC.

PMID: 17058222.

________________________

The primary immune deficiency called IGAD (immunoglobin A deficiency)

seems to be an exception. I have seen papers describing " primary

sclerosing cholangitis " being associated with IGAD, and I wonder

whether these may be closely related. Perhaps PSC has an immunoglubin

A deficiency component to it?

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)

[Guest guest]

Hi ;

I'm very sorry to hear about your husband's hospitalization, and I

hope that he can get quick treatment for his Crohn's flare and

abscess.

The difference between primary sclerosing cholangitis and secondary

sclerosing cholangitis is explained in this article (below).

Basically, secondary sclerosing cholangitis has a known pathological

process, whereas primary sclerosing cholangitis does not. Examples of

secondary sclerosing cholangitis include various primary immune

deficiencies such as hyper-IgM syndrome, immune deficiency caused by

AIDS, sclerosing cholangitis caused by chemotherapy or blunt trauma

to the liver. I believe that there also a form of sclerosing

cholangitis associated with burn injury. If the doctor does not know

the cause, I suppose it may be tempting to just write " sclerosing

cholangitis " . But since PSC is often associated with inflammatory

bowel disease, and your husband has Crohn's disease, I think you

could assume that it is primary sclerosing cholangitis.

________________________________

Hepatology 44: 1063-1074 (2006)

Sclerosing cholangitis: a focus on secondary causes.

Abdalian R, Heathcote EJ

Department of Medicine, University Health Network, Toronto Western

Hospital, University of Toronto, Toronto, Ontario, Canada.

Secondary sclerosing cholangitis (SSC) is a disease that is

morphologically similar to primary sclerosing cholangitis (PSC) but

that originates from a known pathological process. Its clinical and

cholangiographic features may mimic PSC, yet its natural history may

be more favorable if recognition is prompt and appropriate therapy is

introduced. Thus, the diagnosis of PSC requires the exclusion of

secondary causes of sclerosing cholangitis and recognition of

associated conditions that may potentially imitate its classic

cholangiographic features. Well-described causes of SSC include

intraductal stone disease, surgical or blunt abdominal trauma, intra-

arterial chemotherapy, and recurrent pancreatitis. However, a wide

variety of other associations have been reported recently, including

autoimmune pancreatitis, portal biliopathy, eosinophillic and/or mast

cell cholangitis, hepatic inflammatory pseudotumor, recurrent

pyogenic cholangitis, primary immune deficiency, and AIDS-related

cholangiopathy. This article offers a comprehensive review of SSC.

PMID: 17058222.

________________________

The primary immune deficiency called IGAD (immunoglobin A deficiency)

seems to be an exception. I have seen papers describing " primary

sclerosing cholangitis " being associated with IGAD, and I wonder

whether these may be closely related. Perhaps PSC has an immunoglubin

A deficiency component to it?

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)

[Guest guest]

Hi ;

I'm very sorry to hear about your husband's hospitalization, and I

hope that he can get quick treatment for his Crohn's flare and

abscess.

The difference between primary sclerosing cholangitis and secondary

sclerosing cholangitis is explained in this article (below).

Basically, secondary sclerosing cholangitis has a known pathological

process, whereas primary sclerosing cholangitis does not. Examples of

secondary sclerosing cholangitis include various primary immune

deficiencies such as hyper-IgM syndrome, immune deficiency caused by

AIDS, sclerosing cholangitis caused by chemotherapy or blunt trauma

to the liver. I believe that there also a form of sclerosing

cholangitis associated with burn injury. If the doctor does not know

the cause, I suppose it may be tempting to just write " sclerosing

cholangitis " . But since PSC is often associated with inflammatory

bowel disease, and your husband has Crohn's disease, I think you

could assume that it is primary sclerosing cholangitis.

________________________________

Hepatology 44: 1063-1074 (2006)

Sclerosing cholangitis: a focus on secondary causes.

Abdalian R, Heathcote EJ

Department of Medicine, University Health Network, Toronto Western

Hospital, University of Toronto, Toronto, Ontario, Canada.

Secondary sclerosing cholangitis (SSC) is a disease that is

morphologically similar to primary sclerosing cholangitis (PSC) but

that originates from a known pathological process. Its clinical and

cholangiographic features may mimic PSC, yet its natural history may

be more favorable if recognition is prompt and appropriate therapy is

introduced. Thus, the diagnosis of PSC requires the exclusion of

secondary causes of sclerosing cholangitis and recognition of

associated conditions that may potentially imitate its classic

cholangiographic features. Well-described causes of SSC include

intraductal stone disease, surgical or blunt abdominal trauma, intra-

arterial chemotherapy, and recurrent pancreatitis. However, a wide

variety of other associations have been reported recently, including

autoimmune pancreatitis, portal biliopathy, eosinophillic and/or mast

cell cholangitis, hepatic inflammatory pseudotumor, recurrent

pyogenic cholangitis, primary immune deficiency, and AIDS-related

cholangiopathy. This article offers a comprehensive review of SSC.

PMID: 17058222.

________________________

The primary immune deficiency called IGAD (immunoglobin A deficiency)

seems to be an exception. I have seen papers describing " primary

sclerosing cholangitis " being associated with IGAD, and I wonder

whether these may be closely related. Perhaps PSC has an immunoglubin

A deficiency component to it?

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)

[Guest guest]

,

I would very interested in any information that you could provide

regarding the connection between IGAD and PSC. I have been DX with

IGAD and have PSC. My daughter also has IGAD, but thus far does not

have PSC. She is 19 and had to have her gall bladder removed at 14

due to a build of sludge, so I worry about her developing PSC in the

future.

If you could send me the links to any thing you may have on the

IGAD/PSC connection I would be grateful.

Thanks

Dawn

>

>

> The primary immune deficiency called IGAD (immunoglobin A

deficiency)

> seems to be an exception. I have seen papers describing " primary

> sclerosing cholangitis " being associated with IGAD, and I wonder

> whether these may be closely related. Perhaps PSC has an

immunoglubin

> A deficiency component to it?

>

> Best regards,

>

> Dave

> (father of (23); PSC 07/03; UC 08/03)

>

[Guest guest]

,

I would very interested in any information that you could provide

regarding the connection between IGAD and PSC. I have been DX with

IGAD and have PSC. My daughter also has IGAD, but thus far does not

have PSC. She is 19 and had to have her gall bladder removed at 14

due to a build of sludge, so I worry about her developing PSC in the

future.

If you could send me the links to any thing you may have on the

IGAD/PSC connection I would be grateful.

Thanks

Dawn

>

>

> The primary immune deficiency called IGAD (immunoglobin A

deficiency)

> seems to be an exception. I have seen papers describing " primary

> sclerosing cholangitis " being associated with IGAD, and I wonder

> whether these may be closely related. Perhaps PSC has an

immunoglubin

> A deficiency component to it?

>

> Best regards,

>

> Dave

> (father of (23); PSC 07/03; UC 08/03)

>

[Guest guest]

,

I would very interested in any information that you could provide

regarding the connection between IGAD and PSC. I have been DX with

IGAD and have PSC. My daughter also has IGAD, but thus far does not

have PSC. She is 19 and had to have her gall bladder removed at 14

due to a build of sludge, so I worry about her developing PSC in the

future.

If you could send me the links to any thing you may have on the

IGAD/PSC connection I would be grateful.

Thanks

Dawn

>

>

> The primary immune deficiency called IGAD (immunoglobin A

deficiency)

> seems to be an exception. I have seen papers describing " primary

> sclerosing cholangitis " being associated with IGAD, and I wonder

> whether these may be closely related. Perhaps PSC has an

immunoglubin

> A deficiency component to it?

>

> Best regards,

>

> Dave

> (father of (23); PSC 07/03; UC 08/03)

>

[Guest guest]

Dear Dawn;

Here are my thoughts on genetic associations between IgA deficiency and PSC. Sorry if this is a bit repetitive of material I may have posted earlier.

Early reports on PSC and PBC in the 1980's have noted an association between both PSC and PBC in isolated or selective IgA deficiency patients:

Wagner A, Eichmann D 1989 Primary sclerosing cholangitis in isolated IgA deficiency. Schweiz. Med. Wochenschr. 119: 835-838.

Curzio M, Bernasconi G, Gullotta R, Ceriani A, Sala G 1985 Association of ulcerative colitis, sclerosing cholangitis and cholangiocarcinoma in a patient with IgA deficiency. Endoscopy 17: 123-125.

SP, EA, Schafer DF, Hoofnagle JH, Varma RR, Strober W 1986 Selective immunoglobulin A deficiency associated with primary biliary cirrhosis in a family with liver disease. Gastroenterology 90: 283-288.

More recently, IgA deficiency has been associated with type 2 autoimmune hepatitis in children:

Mieli-Vergani G, Vergani D 2008 Autoimmune paediatric liver disease. World J. Gastroenterol. 14: 3360-3367.

Genetic studies indicate that the major genetic risk factor for IgA deficiency resides in the major histocompatibility complex, as does the major genetic risk factor for PSC. In fact, the same haplotype may be involved:

http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=137100

" HLA-A1, B8, DR3, a haplotype associated with selective IgA deficiency"

s EB, Chapman RW 1999 Sclerosing cholangitis. Curr. Opin. Gastroenterol. 15: 436.

"Susceptibility to PSC is associated with the HLA A1-B8-DR3 haplotype"

The involvement of the HLA-DQB1 gene cannot be ruled out in both IgA deficiency and PSC:

Olerup O, CI, Bjorkander J, Hammarstrom L 1992 Shared HLA class II-associated genetic susceptibility and resistance, related to the HLA-DQB1 gene, in IgA deficiency and common variable immunodeficiency. Proc. Natl. Acad. Sci. U.S.A. 89: 10653-10657.

son PT, Norris S 2002 Evaluation of the role of MHC class II alleles, haplotypes and selected amino acid sequences in primary sclerosing cholangitis. Autoimmunity 35: 555-564.

and the HLA-DQB1 gene is a very important determinant of celiac disease:

Jores RD, Frau F, Cucca F, Clemente MG, Orru S, Rais M, De Virgiliis S, Congia M 2007 HLA-DQB1*0201 homozygosis predisposes to severe intestinal damage in celiac disease. Scand. J. Gastroenterol. 42: 48-53.

More recently, the CTLA-4/ICOS gene region has been associated with both celiac disease and IgA deficiency:

Haimila K, Einarsdottir E, Kauwe AD, Koskinen LL, Pan-Hammarstrom Q, Kaartinen T, Kurppa K, Ziberna F, Not T, Vatta S, Ventura A, Korponay-Szabo IR, Adany R, Pocsai Z, Szeles G, Dukes E, Kaukinen K, Maki M, Koskinen S, Partanen J, Hammarstrom L, et al 2008 The shared CTLA4-ICOS risk locus in celiac disease, IgA deficiency and common variable immunodeficiency. Genes Immun. Nov 20 [Epub ahead of print].

and it's known that the CTLA-4 gene is also a susceptibility gene for autoimmune hepatitis and primary biliary cirrhosis:

Agarwal K, Czaja AJ, DE, son PT 2000 Cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphisms and susceptibility to type 1 autoimmune hepatitis. Hepatology 31: 49-53.

Juran BD, Atkinson EJ, Schlicht EM, Fridley BL, Lazaridis KN 2008 Primary biliary cirrhosis is associated with a genetic variant in the 3' flanking region of the CTLA4 gene. Gastroenterology 135: 1200-1206.

It is noteworthy that IgA deficiency is commonly associated with celiac disease:

Heneghan MA, s FM, Cryan EM, Warner RH, McCarthy CF 1997 Celiac sprue and immunodeficiency states: a 25-year review. J. Clin. Gastroenterol. 25: 421-425.

and that celiac disease is in turn commonly associated with PSC, PBC and autoimmune hepatitis:

Volta U 2008 Liver dysfunction in celiac disease. Minerva Med. 99: 619-629.

So, it appears that celiac disease, PSC, AIH, PBC and IgA deficiency may share some common genetic risk factors.

I have some other thoughts on selective IgA deficiency in the gut that may be caused by non-genetic factors and which may play a role in IBD and PSC, but I will not write about these here because it sounds like you are more interested in the genetic aspects? I can very much understand your concern for your daughter's health, but I hope that she does not develop PSC.

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)

[Guest guest]

Dear Dawn;

Here are my thoughts on genetic associations between IgA deficiency and PSC. Sorry if this is a bit repetitive of material I may have posted earlier.

Early reports on PSC and PBC in the 1980's have noted an association between both PSC and PBC in isolated or selective IgA deficiency patients:

Wagner A, Eichmann D 1989 Primary sclerosing cholangitis in isolated IgA deficiency. Schweiz. Med. Wochenschr. 119: 835-838.

Curzio M, Bernasconi G, Gullotta R, Ceriani A, Sala G 1985 Association of ulcerative colitis, sclerosing cholangitis and cholangiocarcinoma in a patient with IgA deficiency. Endoscopy 17: 123-125.

SP, EA, Schafer DF, Hoofnagle JH, Varma RR, Strober W 1986 Selective immunoglobulin A deficiency associated with primary biliary cirrhosis in a family with liver disease. Gastroenterology 90: 283-288.

More recently, IgA deficiency has been associated with type 2 autoimmune hepatitis in children:

Mieli-Vergani G, Vergani D 2008 Autoimmune paediatric liver disease. World J. Gastroenterol. 14: 3360-3367.

Genetic studies indicate that the major genetic risk factor for IgA deficiency resides in the major histocompatibility complex, as does the major genetic risk factor for PSC. In fact, the same haplotype may be involved:

http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=137100

" HLA-A1, B8, DR3, a haplotype associated with selective IgA deficiency"

s EB, Chapman RW 1999 Sclerosing cholangitis. Curr. Opin. Gastroenterol. 15: 436.

"Susceptibility to PSC is associated with the HLA A1-B8-DR3 haplotype"

The involvement of the HLA-DQB1 gene cannot be ruled out in both IgA deficiency and PSC:

Olerup O, CI, Bjorkander J, Hammarstrom L 1992 Shared HLA class II-associated genetic susceptibility and resistance, related to the HLA-DQB1 gene, in IgA deficiency and common variable immunodeficiency. Proc. Natl. Acad. Sci. U.S.A. 89: 10653-10657.

son PT, Norris S 2002 Evaluation of the role of MHC class II alleles, haplotypes and selected amino acid sequences in primary sclerosing cholangitis. Autoimmunity 35: 555-564.

and the HLA-DQB1 gene is a very important determinant of celiac disease:

Jores RD, Frau F, Cucca F, Clemente MG, Orru S, Rais M, De Virgiliis S, Congia M 2007 HLA-DQB1*0201 homozygosis predisposes to severe intestinal damage in celiac disease. Scand. J. Gastroenterol. 42: 48-53.

More recently, the CTLA-4/ICOS gene region has been associated with both celiac disease and IgA deficiency:

Haimila K, Einarsdottir E, Kauwe AD, Koskinen LL, Pan-Hammarstrom Q, Kaartinen T, Kurppa K, Ziberna F, Not T, Vatta S, Ventura A, Korponay-Szabo IR, Adany R, Pocsai Z, Szeles G, Dukes E, Kaukinen K, Maki M, Koskinen S, Partanen J, Hammarstrom L, et al 2008 The shared CTLA4-ICOS risk locus in celiac disease, IgA deficiency and common variable immunodeficiency. Genes Immun. Nov 20 [Epub ahead of print].

and it's known that the CTLA-4 gene is also a susceptibility gene for autoimmune hepatitis and primary biliary cirrhosis:

Agarwal K, Czaja AJ, DE, son PT 2000 Cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphisms and susceptibility to type 1 autoimmune hepatitis. Hepatology 31: 49-53.

Juran BD, Atkinson EJ, Schlicht EM, Fridley BL, Lazaridis KN 2008 Primary biliary cirrhosis is associated with a genetic variant in the 3' flanking region of the CTLA4 gene. Gastroenterology 135: 1200-1206.

It is noteworthy that IgA deficiency is commonly associated with celiac disease:

Heneghan MA, s FM, Cryan EM, Warner RH, McCarthy CF 1997 Celiac sprue and immunodeficiency states: a 25-year review. J. Clin. Gastroenterol. 25: 421-425.

and that celiac disease is in turn commonly associated with PSC, PBC and autoimmune hepatitis:

Volta U 2008 Liver dysfunction in celiac disease. Minerva Med. 99: 619-629.

So, it appears that celiac disease, PSC, AIH, PBC and IgA deficiency may share some common genetic risk factors.

I have some other thoughts on selective IgA deficiency in the gut that may be caused by non-genetic factors and which may play a role in IBD and PSC, but I will not write about these here because it sounds like you are more interested in the genetic aspects? I can very much understand your concern for your daughter's health, but I hope that she does not develop PSC.

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)

[Guest guest]

Dear Dawn;

Here are my thoughts on genetic associations between IgA deficiency and PSC. Sorry if this is a bit repetitive of material I may have posted earlier.

Early reports on PSC and PBC in the 1980's have noted an association between both PSC and PBC in isolated or selective IgA deficiency patients:

Wagner A, Eichmann D 1989 Primary sclerosing cholangitis in isolated IgA deficiency. Schweiz. Med. Wochenschr. 119: 835-838.

Curzio M, Bernasconi G, Gullotta R, Ceriani A, Sala G 1985 Association of ulcerative colitis, sclerosing cholangitis and cholangiocarcinoma in a patient with IgA deficiency. Endoscopy 17: 123-125.

SP, EA, Schafer DF, Hoofnagle JH, Varma RR, Strober W 1986 Selective immunoglobulin A deficiency associated with primary biliary cirrhosis in a family with liver disease. Gastroenterology 90: 283-288.

More recently, IgA deficiency has been associated with type 2 autoimmune hepatitis in children:

Mieli-Vergani G, Vergani D 2008 Autoimmune paediatric liver disease. World J. Gastroenterol. 14: 3360-3367.

Genetic studies indicate that the major genetic risk factor for IgA deficiency resides in the major histocompatibility complex, as does the major genetic risk factor for PSC. In fact, the same haplotype may be involved:

http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=137100

" HLA-A1, B8, DR3, a haplotype associated with selective IgA deficiency"

s EB, Chapman RW 1999 Sclerosing cholangitis. Curr. Opin. Gastroenterol. 15: 436.

"Susceptibility to PSC is associated with the HLA A1-B8-DR3 haplotype"

The involvement of the HLA-DQB1 gene cannot be ruled out in both IgA deficiency and PSC:

Olerup O, CI, Bjorkander J, Hammarstrom L 1992 Shared HLA class II-associated genetic susceptibility and resistance, related to the HLA-DQB1 gene, in IgA deficiency and common variable immunodeficiency. Proc. Natl. Acad. Sci. U.S.A. 89: 10653-10657.

son PT, Norris S 2002 Evaluation of the role of MHC class II alleles, haplotypes and selected amino acid sequences in primary sclerosing cholangitis. Autoimmunity 35: 555-564.

and the HLA-DQB1 gene is a very important determinant of celiac disease:

Jores RD, Frau F, Cucca F, Clemente MG, Orru S, Rais M, De Virgiliis S, Congia M 2007 HLA-DQB1*0201 homozygosis predisposes to severe intestinal damage in celiac disease. Scand. J. Gastroenterol. 42: 48-53.

More recently, the CTLA-4/ICOS gene region has been associated with both celiac disease and IgA deficiency:

Haimila K, Einarsdottir E, Kauwe AD, Koskinen LL, Pan-Hammarstrom Q, Kaartinen T, Kurppa K, Ziberna F, Not T, Vatta S, Ventura A, Korponay-Szabo IR, Adany R, Pocsai Z, Szeles G, Dukes E, Kaukinen K, Maki M, Koskinen S, Partanen J, Hammarstrom L, et al 2008 The shared CTLA4-ICOS risk locus in celiac disease, IgA deficiency and common variable immunodeficiency. Genes Immun. Nov 20 [Epub ahead of print].

and it's known that the CTLA-4 gene is also a susceptibility gene for autoimmune hepatitis and primary biliary cirrhosis:

Agarwal K, Czaja AJ, DE, son PT 2000 Cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphisms and susceptibility to type 1 autoimmune hepatitis. Hepatology 31: 49-53.

Juran BD, Atkinson EJ, Schlicht EM, Fridley BL, Lazaridis KN 2008 Primary biliary cirrhosis is associated with a genetic variant in the 3' flanking region of the CTLA4 gene. Gastroenterology 135: 1200-1206.

It is noteworthy that IgA deficiency is commonly associated with celiac disease:

Heneghan MA, s FM, Cryan EM, Warner RH, McCarthy CF 1997 Celiac sprue and immunodeficiency states: a 25-year review. J. Clin. Gastroenterol. 25: 421-425.

and that celiac disease is in turn commonly associated with PSC, PBC and autoimmune hepatitis:

Volta U 2008 Liver dysfunction in celiac disease. Minerva Med. 99: 619-629.

So, it appears that celiac disease, PSC, AIH, PBC and IgA deficiency may share some common genetic risk factors.

I have some other thoughts on selective IgA deficiency in the gut that may be caused by non-genetic factors and which may play a role in IBD and PSC, but I will not write about these here because it sounds like you are more interested in the genetic aspects? I can very much understand your concern for your daughter's health, but I hope that she does not develop PSC.

Best regards,

Dave

(father of (23); PSC 07/03; UC 08/03)

[Guest guest]

,

Thank you very much for this information. The more knowledge I have

the better I can help her, she is at theat stubburn age where she

won't get check by the doctors. SHe was diagnosed with IGAD at age 3

due to her GI symptoms. They did not Diagnose me until I was in my

30's.

I know there is a link to persons of northern european background and

IGAD, has there been any studies on PSC and northern european

heratiage that you are aware of?

Again Thank You

Dawn

>

>

> Dear Dawn;

>

> Here are my thoughts on genetic associations between IgA deficiency

and

> PSC. Sorry if this is a bit repetitive of material I may have posted

> earlier.

>

> Early reports on PSC and PBC in the 1980's have noted an association

> between both PSC and PBC in isolated or selective IgA deficiency

> patients:

>

> Wagner A, Eichmann D 1989 Primary sclerosing cholangitis in

isolated IgA

> deficiency. Schweiz. Med. Wochenschr. 119: 835-838.

> http://www.ncbi.nlm.nih.gov/pubmed/2672299>

>

> Curzio M, Bernasconi G, Gullotta R, Ceriani A, Sala G 1985

Association

> of ulcerative colitis, sclerosing cholangitis and

cholangiocarcinoma in

> a patient with IgA deficiency. Endoscopy 17: 123-125.

> http://www.ncbi.nlm.nih.gov/pubmed/2988928>

>

> SP, EA, Schafer DF, Hoofnagle JH, Varma RR, Strober W

1986

> Selective immunoglobulin A deficiency associated with primary

biliary

> cirrhosis in a family with liver disease. Gastroenterology 90: 283-

288.

> http://www.ncbi.nlm.nih.gov/pubmed/2934289>

>

> More recently, IgA deficiency has been associated with type 2

autoimmune

> hepatitis in children:

>

> Mieli-Vergani G, Vergani D 2008 Autoimmune paediatric liver disease.

> World J. Gastroenterol. 14: 3360-3367.

> http://www.ncbi.nlm.nih.gov/pubmed/18528933>

>

> Genetic studies indicate that the major genetic risk factor for IgA

> deficiency resides in the major histocompatibility complex, as does

the

> major genetic risk factor for PSC. In fact, the same haplotype may

be

> involved:

>

> http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=137100

> http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=137100>

>

> " HLA-A1, B8, DR3, a haplotype associated with selective IgA

deficiency "

>

> s EB, Chapman RW 1999 Sclerosing cholangitis. Curr. Opin.

> Gastroenterol. 15: 436.

http://www.ncbi.nlm.nih.gov/pubmed/17023986>

>

> " Susceptibility to PSC is associated with the HLA A1-B8-DR3

haplotype "

>

> The involvement of the HLA-DQB1 gene cannot be ruled out in both IgA

> deficiency and PSC:

>

> Olerup O, CI, Bjorkander J, Hammarstrom L 1992 Shared HLA

class

> II-associated genetic susceptibility and resistance, related to the

> HLA-DQB1 gene, in IgA deficiency and common variable

immunodeficiency.

> Proc. Natl. Acad. Sci. U.S.A. 89: 10653-10657.

> http://www.ncbi.nlm.nih.gov/pubmed/1438261>

>

> son PT, Norris S 2002 Evaluation of the role of MHC class II

> alleles, haplotypes and selected amino acid sequences in primary

> sclerosing cholangitis. Autoimmunity 35: 555-564.

> http://www.ncbi.nlm.nih.gov/pubmed/12765483>

>

> and the HLA-DQB1 gene is a very important determinant of celiac

disease:

>

> Jores RD, Frau F, Cucca F, Clemente MG, Orru S, Rais M, De

Virgiliis S,

> Congia M 2007 HLA-DQB1*0201 homozygosis predisposes to severe

intestinal

> damage in celiac disease. Scand. J. Gastroenterol. 42: 48-53.

> http://www.ncbi.nlm.nih.gov/pubmed/17190762>

>

> More recently, the CTLA-4/ICOS gene region has been associated with

both

> celiac disease and IgA deficiency:

>

> Haimila K, Einarsdottir E, Kauwe AD, Koskinen LL, Pan-Hammarstrom Q,

> Kaartinen T, Kurppa K, Ziberna F, Not T, Vatta S, Ventura A,

> Korponay-Szabo IR, Adany R, Pocsai Z, Szeles G, Dukes E, Kaukinen K,

> Maki M, Koskinen S, Partanen J, Hammarstrom L, et al 2008 The shared

> CTLA4-ICOS risk locus in celiac disease, IgA deficiency and common

> variable immunodeficiency. Genes Immun. Nov 20 [Epub ahead of

print].

> http://www.ncbi.nlm.nih.gov/pubmed/19020530>

>

> and it's known that the CTLA-4 gene is also a susceptibility gene

for

> autoimmune hepatitis and primary biliary cirrhosis:

>

> Agarwal K, Czaja AJ, DE, son PT 2000 Cytotoxic T

lymphocyte

> antigen-4 (CTLA-4) gene polymorphisms and susceptibility to type 1

> autoimmune hepatitis. Hepatology 31: 49-53.

> http://www.ncbi.nlm.nih.gov/pubmed/10613727>

>

> Juran BD, Atkinson EJ, Schlicht EM, Fridley BL, Lazaridis KN 2008

> Primary biliary cirrhosis is associated with a genetic variant in

the 3'

> flanking region of the CTLA4 gene. Gastroenterology 135: 1200-1206.

> http://www.ncbi.nlm.nih.gov/pubmed/18778710>

>

> It is noteworthy that IgA deficiency is commonly associated with

celiac

> disease:

>

> Heneghan MA, s FM, Cryan EM, Warner RH, McCarthy CF 1997

Celiac

> sprue and immunodeficiency states: a 25-year review. J. Clin.

> Gastroenterol. 25: 421-425.

http://www.ncbi.nlm.nih.gov/pubmed/9412941>

>

> and that celiac disease is in turn commonly associated with PSC,

PBC and

> autoimmune hepatitis:

>

> Volta U 2008 Liver dysfunction in celiac disease. Minerva Med. 99:

> 619-629. http://www.ncbi.nlm.nih.gov/pubmed/19034259>

>

> So, it appears that celiac disease, PSC, AIH, PBC and IgA

deficiency may

> share some common genetic risk factors.

>

> I have some other thoughts on selective IgA deficiency in the gut

that

> may be caused by non-genetic factors and which may play a role in

IBD

> and PSC, but I will not write about these here because it sounds

like

> you are more interested in the genetic aspects? I can very much

> understand your concern for your daughter's health, but I hope that

she

> does not develop PSC.

>

> Best regards,

>

> Dave

>

> (father of (23); PSC 07/03; UC 08/03)

>

[Guest guest]

,

Thank you very much for this information. The more knowledge I have

the better I can help her, she is at theat stubburn age where she

won't get check by the doctors. SHe was diagnosed with IGAD at age 3

due to her GI symptoms. They did not Diagnose me until I was in my

30's.

I know there is a link to persons of northern european background and

IGAD, has there been any studies on PSC and northern european

heratiage that you are aware of?

Again Thank You

Dawn

>

>

> Dear Dawn;

>

> Here are my thoughts on genetic associations between IgA deficiency

and

> PSC. Sorry if this is a bit repetitive of material I may have posted

> earlier.

>

> Early reports on PSC and PBC in the 1980's have noted an association

> between both PSC and PBC in isolated or selective IgA deficiency

> patients:

>

> Wagner A, Eichmann D 1989 Primary sclerosing cholangitis in

isolated IgA

> deficiency. Schweiz. Med. Wochenschr. 119: 835-838.

> http://www.ncbi.nlm.nih.gov/pubmed/2672299>

>

> Curzio M, Bernasconi G, Gullotta R, Ceriani A, Sala G 1985

Association

> of ulcerative colitis, sclerosing cholangitis and

cholangiocarcinoma in

> a patient with IgA deficiency. Endoscopy 17: 123-125.

> http://www.ncbi.nlm.nih.gov/pubmed/2988928>

>

> SP, EA, Schafer DF, Hoofnagle JH, Varma RR, Strober W

1986

> Selective immunoglobulin A deficiency associated with primary

biliary

> cirrhosis in a family with liver disease. Gastroenterology 90: 283-

288.

> http://www.ncbi.nlm.nih.gov/pubmed/2934289>

>

> More recently, IgA deficiency has been associated with type 2

autoimmune

> hepatitis in children:

>

> Mieli-Vergani G, Vergani D 2008 Autoimmune paediatric liver disease.

> World J. Gastroenterol. 14: 3360-3367.

> http://www.ncbi.nlm.nih.gov/pubmed/18528933>

>

> Genetic studies indicate that the major genetic risk factor for IgA

> deficiency resides in the major histocompatibility complex, as does

the

> major genetic risk factor for PSC. In fact, the same haplotype may

be

> involved:

>

> http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=137100

> http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=137100>

>

> " HLA-A1, B8, DR3, a haplotype associated with selective IgA

deficiency "

>

> s EB, Chapman RW 1999 Sclerosing cholangitis. Curr. Opin.

> Gastroenterol. 15: 436.

http://www.ncbi.nlm.nih.gov/pubmed/17023986>

>

> " Susceptibility to PSC is associated with the HLA A1-B8-DR3

haplotype "

>

> The involvement of the HLA-DQB1 gene cannot be ruled out in both IgA

> deficiency and PSC:

>

> Olerup O, CI, Bjorkander J, Hammarstrom L 1992 Shared HLA

class

> II-associated genetic susceptibility and resistance, related to the

> HLA-DQB1 gene, in IgA deficiency and common variable

immunodeficiency.

> Proc. Natl. Acad. Sci. U.S.A. 89: 10653-10657.

> http://www.ncbi.nlm.nih.gov/pubmed/1438261>

>

> son PT, Norris S 2002 Evaluation of the role of MHC class II

> alleles, haplotypes and selected amino acid sequences in primary

> sclerosing cholangitis. Autoimmunity 35: 555-564.

> http://www.ncbi.nlm.nih.gov/pubmed/12765483>

>

> and the HLA-DQB1 gene is a very important determinant of celiac

disease:

>

> Jores RD, Frau F, Cucca F, Clemente MG, Orru S, Rais M, De

Virgiliis S,

> Congia M 2007 HLA-DQB1*0201 homozygosis predisposes to severe

intestinal

> damage in celiac disease. Scand. J. Gastroenterol. 42: 48-53.

> http://www.ncbi.nlm.nih.gov/pubmed/17190762>

>

> More recently, the CTLA-4/ICOS gene region has been associated with

both

> celiac disease and IgA deficiency:

>

> Haimila K, Einarsdottir E, Kauwe AD, Koskinen LL, Pan-Hammarstrom Q,

> Kaartinen T, Kurppa K, Ziberna F, Not T, Vatta S, Ventura A,

> Korponay-Szabo IR, Adany R, Pocsai Z, Szeles G, Dukes E, Kaukinen K,

> Maki M, Koskinen S, Partanen J, Hammarstrom L, et al 2008 The shared

> CTLA4-ICOS risk locus in celiac disease, IgA deficiency and common

> variable immunodeficiency. Genes Immun. Nov 20 [Epub ahead of

print].

> http://www.ncbi.nlm.nih.gov/pubmed/19020530>

>

> and it's known that the CTLA-4 gene is also a susceptibility gene

for

> autoimmune hepatitis and primary biliary cirrhosis:

>

> Agarwal K, Czaja AJ, DE, son PT 2000 Cytotoxic T

lymphocyte

> antigen-4 (CTLA-4) gene polymorphisms and susceptibility to type 1

> autoimmune hepatitis. Hepatology 31: 49-53.

> http://www.ncbi.nlm.nih.gov/pubmed/10613727>

>

> Juran BD, Atkinson EJ, Schlicht EM, Fridley BL, Lazaridis KN 2008

> Primary biliary cirrhosis is associated with a genetic variant in

the 3'

> flanking region of the CTLA4 gene. Gastroenterology 135: 1200-1206.

> http://www.ncbi.nlm.nih.gov/pubmed/18778710>

>

> It is noteworthy that IgA deficiency is commonly associated with

celiac

> disease:

>

> Heneghan MA, s FM, Cryan EM, Warner RH, McCarthy CF 1997

Celiac

> sprue and immunodeficiency states: a 25-year review. J. Clin.

> Gastroenterol. 25: 421-425.

http://www.ncbi.nlm.nih.gov/pubmed/9412941>

>

> and that celiac disease is in turn commonly associated with PSC,

PBC and

> autoimmune hepatitis:

>

> Volta U 2008 Liver dysfunction in celiac disease. Minerva Med. 99:

> 619-629. http://www.ncbi.nlm.nih.gov/pubmed/19034259>

>

> So, it appears that celiac disease, PSC, AIH, PBC and IgA

deficiency may

> share some common genetic risk factors.

>

> I have some other thoughts on selective IgA deficiency in the gut

that

> may be caused by non-genetic factors and which may play a role in

IBD

> and PSC, but I will not write about these here because it sounds

like

> you are more interested in the genetic aspects? I can very much

> understand your concern for your daughter's health, but I hope that

she

> does not develop PSC.

>

> Best regards,

>

> Dave

>

> (father of (23); PSC 07/03; UC 08/03)

>

[Guest guest]

Hi Dawn;

This article covers the topic of incidence and prevalence of PSC in Northern Europe:

LaRusso NF, Shneider BL, Black D, Gores GJ, SP, Doo E, Hoofnagle JH 2006 Primary sclerosing cholangitis: summary of a workshop. Hepatology 44: 746-764

"There have been few population-based epidemiological studies of PSC (Table 3). The incidence is 0.9 to 1.3 per 100,000 in Northern Europe 10,32,33 and the United States 6 but less than 0.1 per 100,000 in Southern Europe 34 and Asia. 35 Patients with PSC survive for an average of 12 to 17 years, so that the prevalence of this disease in these same surveys ranges from 8 to 14 per 100,000 persons in Northern Europe and the United States, but is 1.3 or less in Southern Europe and Asia. The frequency of PSC in Africa is unknown and there have been no large studies of PSC in minority U.S. populations (Asians and African Americans). PSC appears to be rare among Native Alaskans. 36 The incidence and prevalence of PSC (1.3 and 8.5 per 100,000 in Oslo, Norway) is somewhat less than that for primary biliary cirrhosis (1.6 and 14.6 per 100,000) and autoimmune hepatitis (1.9 and 16.9 per 100,000). 32"

I honestly don't know what the contribution of genetics is to this relationship. Perhaps there is also an environental influence at work (e.g. vitamin D status in relation to latitude):

Huotari A, Herzig KH 2008 Vitamin D and living in northern latitudes - an endemic risk area for vitamin D deficiency. Int. J. Circumpolar Health 67: 164-178.

Best regards,

Dave R.

> I know there is a link to persons of northern european background and > IGAD, has there been any studies on PSC and northern european > heratiage that you are aware of?

[Guest guest]

Hi Dawn;

This article covers the topic of incidence and prevalence of PSC in Northern Europe:

LaRusso NF, Shneider BL, Black D, Gores GJ, SP, Doo E, Hoofnagle JH 2006 Primary sclerosing cholangitis: summary of a workshop. Hepatology 44: 746-764

"There have been few population-based epidemiological studies of PSC (Table 3). The incidence is 0.9 to 1.3 per 100,000 in Northern Europe 10,32,33 and the United States 6 but less than 0.1 per 100,000 in Southern Europe 34 and Asia. 35 Patients with PSC survive for an average of 12 to 17 years, so that the prevalence of this disease in these same surveys ranges from 8 to 14 per 100,000 persons in Northern Europe and the United States, but is 1.3 or less in Southern Europe and Asia. The frequency of PSC in Africa is unknown and there have been no large studies of PSC in minority U.S. populations (Asians and African Americans). PSC appears to be rare among Native Alaskans. 36 The incidence and prevalence of PSC (1.3 and 8.5 per 100,000 in Oslo, Norway) is somewhat less than that for primary biliary cirrhosis (1.6 and 14.6 per 100,000) and autoimmune hepatitis (1.9 and 16.9 per 100,000). 32"

I honestly don't know what the contribution of genetics is to this relationship. Perhaps there is also an environental influence at work (e.g. vitamin D status in relation to latitude):

Huotari A, Herzig KH 2008 Vitamin D and living in northern latitudes - an endemic risk area for vitamin D deficiency. Int. J. Circumpolar Health 67: 164-178.

Best regards,

Dave R.

> I know there is a link to persons of northern european background and > IGAD, has there been any studies on PSC and northern european > heratiage that you are aware of?

[Guest guest]

Thank you very much .

What makes you question vitamin D. I am curious. They check mine a

lot and so far it has remained normal. My B-12 is low and vitamin A

drops at times.

Dawn

> > I know there is a link to persons of northern european background

and

> > IGAD, has there been any studies on PSC and northern european

> > heratiage that you are aware of?

>

[Guest guest]

Thank you very much .

What makes you question vitamin D. I am curious. They check mine a

lot and so far it has remained normal. My B-12 is low and vitamin A

drops at times.

Dawn

> > I know there is a link to persons of northern european background

and

> > IGAD, has there been any studies on PSC and northern european

> > heratiage that you are aware of?

>

[Guest guest]

Thank you very much .

What makes you question vitamin D. I am curious. They check mine a

lot and so far it has remained normal. My B-12 is low and vitamin A

drops at times.

Dawn

> > I know there is a link to persons of northern european background

and

> > IGAD, has there been any studies on PSC and northern european

> > heratiage that you are aware of?

>

[Guest guest]

Maybe it has to do with the food they eat. ) lots of fish & seaweed. Just a thought.

http://www.alaskawildberryproducts.com/education/alaskan-foods.html

Lori A.

"Aggressively Pursuing Solutions To Your Real Estate Needs!"

First Weber Group

Cell:

1507 E. Sunset Drive

Waukesha, WI 53189

LoriUSA@...

www.Lori.FirstWeber.com

To: Sent: Sunday, February 1, 2009 2:40:04 PMSubject: Re: scelorsing colangitis/primary versus secondary

Hi Dawn;

This article covers the topic of incidence and prevalence of PSC in Northern Europe:

LaRusso NF, Shneider BL, Black D, Gores GJ, SP, Doo E, Hoofnagle JH 2006 Primary sclerosing cholangitis: summary of a workshop. Hepatology 44: 746-764

"There have been few population-based epidemiological studies of PSC (Table 3). The incidence is 0.9 to 1.3 per 100,000 in Northern Europe 10,32,33 and the United States 6 but less than 0.1 per 100,000 in Southern Europe 34 and Asia. 35 Patients with PSC survive for an average of 12 to 17 years, so that the prevalence of this disease in these same surveys ranges from 8 to 14 per 100,000 persons in Northern Europe and the United States, but is 1.3 or less in Southern Europe and Asia. The frequency of PSC in Africa is unknown and there have been no large studies of PSC

in minority U.S. populations (Asians and African Americans). PSC appears to be rare among Native Alaskans. 36 The incidence and prevalence of PSC (1.3 and 8.5 per 100,000 in Oslo, Norway) is somewhat less than that for primary biliary cirrhosis (1.6 and 14.6 per 100,000) and autoimmune hepatitis (1.9 and 16.9 per 100,000). 32"

I honestly don't know what the contribution of genetics is to this relationship. Perhaps there is also an environental influence at work (e.g. vitamin D status in relation to latitude):

Huotari A, Herzig KH 2008 Vitamin D and living in northern latitudes - an endemic risk area for vitamin D deficiency. Int. J. Circumpolar Health 67: 164-178.

Best regards,

Dave R.

> I know there is a link to persons of northern european background and > IGAD, has there been any studies on PSC and northern european > heratiage that you are aware of?

[Guest guest]

Maybe it has to do with the food they eat. ) lots of fish & seaweed. Just a thought.

http://www.alaskawildberryproducts.com/education/alaskan-foods.html

Lori A.

"Aggressively Pursuing Solutions To Your Real Estate Needs!"

First Weber Group

Cell:

1507 E. Sunset Drive

Waukesha, WI 53189

LoriUSA@...

www.Lori.FirstWeber.com

To: Sent: Sunday, February 1, 2009 2:40:04 PMSubject: Re: scelorsing colangitis/primary versus secondary

Hi Dawn;

This article covers the topic of incidence and prevalence of PSC in Northern Europe:

LaRusso NF, Shneider BL, Black D, Gores GJ, SP, Doo E, Hoofnagle JH 2006 Primary sclerosing cholangitis: summary of a workshop. Hepatology 44: 746-764

"There have been few population-based epidemiological studies of PSC (Table 3). The incidence is 0.9 to 1.3 per 100,000 in Northern Europe 10,32,33 and the United States 6 but less than 0.1 per 100,000 in Southern Europe 34 and Asia. 35 Patients with PSC survive for an average of 12 to 17 years, so that the prevalence of this disease in these same surveys ranges from 8 to 14 per 100,000 persons in Northern Europe and the United States, but is 1.3 or less in Southern Europe and Asia. The frequency of PSC in Africa is unknown and there have been no large studies of PSC

in minority U.S. populations (Asians and African Americans). PSC appears to be rare among Native Alaskans. 36 The incidence and prevalence of PSC (1.3 and 8.5 per 100,000 in Oslo, Norway) is somewhat less than that for primary biliary cirrhosis (1.6 and 14.6 per 100,000) and autoimmune hepatitis (1.9 and 16.9 per 100,000). 32"

I honestly don't know what the contribution of genetics is to this relationship. Perhaps there is also an environental influence at work (e.g. vitamin D status in relation to latitude):

Huotari A, Herzig KH 2008 Vitamin D and living in northern latitudes - an endemic risk area for vitamin D deficiency. Int. J. Circumpolar Health 67: 164-178.

Best regards,

Dave R.

> I know there is a link to persons of northern european background and > IGAD, has there been any studies on PSC and northern european > heratiage that you are aware of?

[Guest guest]

Maybe it has to do with the food they eat. ) lots of fish & seaweed. Just a thought.

http://www.alaskawildberryproducts.com/education/alaskan-foods.html

Lori A.

"Aggressively Pursuing Solutions To Your Real Estate Needs!"

First Weber Group

Cell:

1507 E. Sunset Drive

Waukesha, WI 53189

LoriUSA@...

www.Lori.FirstWeber.com

To: Sent: Sunday, February 1, 2009 2:40:04 PMSubject: Re: scelorsing colangitis/primary versus secondary

Hi Dawn;

This article covers the topic of incidence and prevalence of PSC in Northern Europe:

LaRusso NF, Shneider BL, Black D, Gores GJ, SP, Doo E, Hoofnagle JH 2006 Primary sclerosing cholangitis: summary of a workshop. Hepatology 44: 746-764

"There have been few population-based epidemiological studies of PSC (Table 3). The incidence is 0.9 to 1.3 per 100,000 in Northern Europe 10,32,33 and the United States 6 but less than 0.1 per 100,000 in Southern Europe 34 and Asia. 35 Patients with PSC survive for an average of 12 to 17 years, so that the prevalence of this disease in these same surveys ranges from 8 to 14 per 100,000 persons in Northern Europe and the United States, but is 1.3 or less in Southern Europe and Asia. The frequency of PSC in Africa is unknown and there have been no large studies of PSC

in minority U.S. populations (Asians and African Americans). PSC appears to be rare among Native Alaskans. 36 The incidence and prevalence of PSC (1.3 and 8.5 per 100,000 in Oslo, Norway) is somewhat less than that for primary biliary cirrhosis (1.6 and 14.6 per 100,000) and autoimmune hepatitis (1.9 and 16.9 per 100,000). 32"

I honestly don't know what the contribution of genetics is to this relationship. Perhaps there is also an environental influence at work (e.g. vitamin D status in relation to latitude):

Huotari A, Herzig KH 2008 Vitamin D and living in northern latitudes - an endemic risk area for vitamin D deficiency. Int. J. Circumpolar Health 67: 164-178.

Best regards,

Dave R.

> I know there is a link to persons of northern european background and > IGAD, has there been any studies on PSC and northern european > heratiage that you are aware of?

[Guest guest]

Thank you for your info. You definitly answered my question.

michelle