Re: IgA Deficiency and PSC? any Information

September 17, 2008

Hi Dawn;

There's a type of IgA deficiency called X-linked hyper-IgM syndrome

that is often associated with sclerosing cholangitis. But this also

comes with low IgG, and IgE as well as low IgA. Have you been tested

for this type?

_________________________________________

J Formos Med Assoc. 2005 Jun;104(6):421-6.

Recurrent acalculous cholecystitis and sclerosing cholangitis in a

patient with X-linked hyper-immunoglobulin M syndrome.

Lin SC, Shyur SD, Ma YC, Huang LH, Lee HC, Lee WI

Division of Allergy and Immunology, Department of Pediatrics, Mackay

Memorial Hospital, Taipei, Taiwan.

X-linked hyper-immunoglobulin M (IgM) syndrome (XHIGM) is a rare

genetic primary immunodeficiency disease caused by mutations of the

CD40 ligand (CD40L) gene with normal or elevated levels of IgM and

markedly decreased serum IgG, IgA, and IgE. Liver disease may occur

as a clinical manifestation in XHIGM. This complication appears to

increase with age. We report an 18-year-old male patient who had

recurrent episodes of acalculous cholecystitis (AC) and sclerosing

cholangitis (SC). The diagnosis of XHIGM was confirmed by the finding

of CD40L expression < 1% of normal and a tyrosine 169 asparaginase

(t526a) mutation in exon 5 (the tumor necrosis factor domain) of the

CD40L gene. The patient had direct hyperbilirubinemia (direct

bilirubin 5.5 mg/dL, total bilirubin 8.7 mg/dL), cholestasis

(alkaline phosphatase 1133 U/L, gamma-glutamyl transferase 1019 U/L)

and elevated transaminases (aspartate aminotransferase 70 U/L,

alanine aminotransferase 101 U/L). Findings on abdominal ultrasound

and abdominal computed tomography were compatible with AC. After the

fourth episode of cholecystitis, cholecystectomy and liver biopsy

were performed. Operative cholangiography revealed poor opacification

of the hepatic duct and proximal common bile duct; the upstream

intrahepatic bile ducts were not visualized. The biopsy specimen

showed marked fibrosis of the portal areas. Enterococcus species was

cultured from the bile. Children or adolescents with recurrent AC and

SC should be evaluated for an underlying immunodeficiency syndrome

such as XHIGM. PMID: 16037832.

_________________________________________

If you have " isolated " IgA deficiency (i.e normal levels of IgG and

IgE), then this too may also be associated with PSC:

_________________________________________

Schweiz Med Wochenschr. 1989 Jun 10;119(23):835-8.

Primary sclerosing cholangitis in isolated IgA deficiency.

Wagner A, Eichmann D.

I. Medizinische Klinik, Landkrankenhaus Coburg.

Primary sclerosing cholangitis was diagnosed in a patient with

isolated IgA deficiency. Similar reports in the literature suggest

that the two conditions are related. Patients with primary sclerosing

cholangitis associated with isolated IgA deficiency are distinguished

by the fact that it is mainly the intrahepatic bile ducts that are

narrowed by the fibrosing process. The disease manifests itself

comparatively early. Recurrent bouts of fever, in combination with

elevated AP, can become the leading symptom even before the onset of

jaundice. The prognosis seems somewhat more favourable than in other

patients with primary sclerosing cholangitis. PMID: 2672299.

_________________________________________

In terms of copper, there is a lot of evidence that copper can

accumulate in the liver in PSC patients, see for example:

_________________________________________

Scand J Gastroenterol. 1995 Dec;30(12):1200-3.

Hepatic retention of copper and selenium in primary sclerosing

cholangitis.

Aaseth J, sen Y, Aadland E, Fausa O, Schrumpf E

Dept. of Clinical Chemistry, Hedmark Central Hospital, Norway.

BACKGROUND: Previous studies have suggested abnormal copper

metabolism in patients with primary sclerosing cholangitis (PSC). In

the present work the trace element metabolism was studied in a group

of 32 patients with PSC. METHODS: Hepatic copper and selenium

concentrations were determined with a sensitive electrothermal atomic

absorption technique. Serum concentrations of copper and zinc were

determined by conventional atomic absorption. RESULTS: For the

patient group serum copper values (20.3 +/- 4.5 mumol/l) were higher

than those for the control group (14 +/- 3 mumol/l), and average

hepatic copper concentrations were greater by a factor of four. Serum

selenium values were slightly lower, although the average hepatic

selenium was significantly higher than in the healthy control group.

Previous studies have discussed possible toxic effects of

hepatocellular copper accumulation, which may be accompanied by

formation of activated oxygen species and depletion of glutathione.

In the present study, however, it could not be demonstrated that the

concentration of the lipoperoxidation product, malonic dialdehyde,

was higher than normal in blood. Furthermore, blood concentrations of

glutathione and glutathione peroxidase were not abnormal. CONCLUSION:

Although a protective effect of the raised selenium concentrations in

the liver might be discussed, it is apparent that the copper

accumulation in the liver cells described here did not induce

detectable changes in the indices studied. PMID: 9053974.

_________________________________________

So it's often easy to mistake PSC for 's disease:

http://www.nlm.nih.gov/medlineplus/ency/article/000785.htm

most often caused by a deficiency of serum ceruloplasmin.

It may be that you doctor wants to be sure that you don't have

's disease, and so wants to check ceruloplasmin level.

Best regards,

Dave

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

September 17, 2008

Thanks for the informarion. As of my last level check my IGG and IGM

were in the lower end of normal, but my doctor says this could change

into a deficency at some point or maybe not

Dawn

In , " "

wrote:

>

> Hi Dawn;

>

> There's a type of IgA deficiency called X-linked hyper-IgM syndrome

> that is often associated with sclerosing cholangitis. But this also

> comes with low IgG, and IgE as well as low IgA. Have you been

tested

> for this type?

> _________________________________________

>

> J Formos Med Assoc. 2005 Jun;104(6):421-6.

>

> Recurrent acalculous cholecystitis and sclerosing cholangitis in a

> patient with X-linked hyper-immunoglobulin M syndrome.

>

> Lin SC, Shyur SD, Ma YC, Huang LH, Lee HC, Lee WI

>

> Division of Allergy and Immunology, Department of Pediatrics,

Mackay

> Memorial Hospital, Taipei, Taiwan.

>

> X-linked hyper-immunoglobulin M (IgM) syndrome (XHIGM) is a rare

> genetic primary immunodeficiency disease caused by mutations of the

> CD40 ligand (CD40L) gene with normal or elevated levels of IgM and

> markedly decreased serum IgG, IgA, and IgE. Liver disease may occur

> as a clinical manifestation in XHIGM. This complication appears to

> increase with age. We report an 18-year-old male patient who had

> recurrent episodes of acalculous cholecystitis (AC) and sclerosing

> cholangitis (SC). The diagnosis of XHIGM was confirmed by the

finding

> of CD40L expression < 1% of normal and a tyrosine 169 asparaginase

> (t526a) mutation in exon 5 (the tumor necrosis factor domain) of

the

> CD40L gene. The patient had direct hyperbilirubinemia (direct

> bilirubin 5.5 mg/dL, total bilirubin 8.7 mg/dL), cholestasis

> (alkaline phosphatase 1133 U/L, gamma-glutamyl transferase 1019

U/L)

> and elevated transaminases (aspartate aminotransferase 70 U/L,

> alanine aminotransferase 101 U/L). Findings on abdominal ultrasound

> and abdominal computed tomography were compatible with AC. After

the

> fourth episode of cholecystitis, cholecystectomy and liver biopsy

> were performed. Operative cholangiography revealed poor

opacification

> of the hepatic duct and proximal common bile duct; the upstream

> intrahepatic bile ducts were not visualized. The biopsy specimen

> showed marked fibrosis of the portal areas. Enterococcus species

was

> cultured from the bile. Children or adolescents with recurrent AC

and

> SC should be evaluated for an underlying immunodeficiency syndrome

> such as XHIGM. PMID: 16037832.

> _________________________________________

>

> If you have " isolated " IgA deficiency (i.e normal levels of IgG and

> IgE), then this too may also be associated with PSC:

> _________________________________________

>

> Schweiz Med Wochenschr. 1989 Jun 10;119(23):835-8.

>

> Primary sclerosing cholangitis in isolated IgA deficiency.

> Wagner A, Eichmann D.

>

> I. Medizinische Klinik, Landkrankenhaus Coburg.

>

> Primary sclerosing cholangitis was diagnosed in a patient with

> isolated IgA deficiency. Similar reports in the literature suggest

> that the two conditions are related. Patients with primary

sclerosing

> cholangitis associated with isolated IgA deficiency are

distinguished

> by the fact that it is mainly the intrahepatic bile ducts that are

> narrowed by the fibrosing process. The disease manifests itself

> comparatively early. Recurrent bouts of fever, in combination with

> elevated AP, can become the leading symptom even before the onset

of

> jaundice. The prognosis seems somewhat more favourable than in

other

> patients with primary sclerosing cholangitis. PMID: 2672299.

> _________________________________________

>

> In terms of copper, there is a lot of evidence that copper can

> accumulate in the liver in PSC patients, see for example:

> _________________________________________

>

> Scand J Gastroenterol. 1995 Dec;30(12):1200-3.

>

> Hepatic retention of copper and selenium in primary sclerosing

> cholangitis.

>

> Aaseth J, sen Y, Aadland E, Fausa O, Schrumpf E

>

> Dept. of Clinical Chemistry, Hedmark Central Hospital, Norway.

>

> BACKGROUND: Previous studies have suggested abnormal copper

> metabolism in patients with primary sclerosing cholangitis (PSC).

In

> the present work the trace element metabolism was studied in a

group

> of 32 patients with PSC. METHODS: Hepatic copper and selenium

> concentrations were determined with a sensitive electrothermal

atomic

> absorption technique. Serum concentrations of copper and zinc were

> determined by conventional atomic absorption. RESULTS: For the

> patient group serum copper values (20.3 +/- 4.5 mumol/l) were

higher

> than those for the control group (14 +/- 3 mumol/l), and average

> hepatic copper concentrations were greater by a factor of four.

Serum

> selenium values were slightly lower, although the average hepatic

> selenium was significantly higher than in the healthy control

group.

> Previous studies have discussed possible toxic effects of

> hepatocellular copper accumulation, which may be accompanied by

> formation of activated oxygen species and depletion of glutathione.

> In the present study, however, it could not be demonstrated that

the

> concentration of the lipoperoxidation product, malonic dialdehyde,

> was higher than normal in blood. Furthermore, blood concentrations

of

> glutathione and glutathione peroxidase were not abnormal.

CONCLUSION:

> Although a protective effect of the raised selenium concentrations

in

> the liver might be discussed, it is apparent that the copper

> accumulation in the liver cells described here did not induce

> detectable changes in the indices studied. PMID: 9053974.

> _________________________________________

>

> So it's often easy to mistake PSC for 's disease:

>

> http://www.nlm.nih.gov/medlineplus/ency/article/000785.htm

>

> most often caused by a deficiency of serum ceruloplasmin.

>

> It may be that you doctor wants to be sure that you don't have

> 's disease, and so wants to check ceruloplasmin level.

>

> Best regards,

>

> Dave

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

>

September 17, 2008