Immunological Study of Children Born to Mothers with Systemic Lupus Erythematosus (SLE)

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Immunological Study of Children Born to Mothers with Systemic Lupus

Erythematosus (SLE)

Category:  25 SLE‹human etiology and pathogenesis

Toru Fukazawa, Mika Hirashima, Makio Kusaoi, Takahiro Morita, Kwangseok Yan,

Hiroshi Hashimoto

Juntendo University School of Medicine, Tokyo, Japan

Presentation Number: 688

Poster Board Number: 153

Keywords: Children born to mothers with SLE, genetic factors, anti-nuclear

antibody

(OBJECTIVE)To evaluate the immunological abnormalities before the onset of

SLE and to find implications for the etiology of SLE, the prospective study

of the children born to mothers with SLE was performed. (PATIENTS AND

METHODS)In a total 288 children born to mothers with SLE, who ranged from

0-25 years in age, anti-nuclear antibodies(ANA)were assayed 6 times in

1991-2001. ANA were assayed by the fluorescence antibody method using Hep2

cells, and subjects showing titers of 40 times the normal value or above

were considered to be positive. Cell surface markers on peripheral blood

lymphocytes were analyzed by flowcytometry. (RESULTS)The frequency of

positivity for ANA was significantly higher in children born to mothers with

SLE(ANA positive in 82 out of 288children)than in controls whose mothers did

not have SLE(ANA positive in 4 out of 54 children). ANA titers as high as

320 times the normal value were detected in 11 children and all of these

children were born from SLE mothers. The male-to-female ratio of

ANA-positive children born to mothers with SLE was about 1:3. A total of 58

children born to mothers with SLE were investigated over time during the

study period. Among them, 15 became positive for ANA and this occurred at

between the age of 4 and 8 years in 9 of them. To evaluate if there were

immunological changes specific for children born to mothers with SLE in this

period, the phenotype of T and B cells in 74 children born to mothers with

SLE and controls from the age 1 to 10 years were analyzed by flowcytometry.

The CD4/CD8 ratios was significantly decreased in children born to mothers

with SLE at an age of 3-4 years and was significantly lower in children born

to mothers with SLE who were positive for ANA than in those negative for

ANA. The expression of Fas, CD80 and CD86 on T cells were significantly

lower in children born to mothers with SLE than in controls. It was reported

that in the SLE model mouse, Fas expression on CD5-positive B cells is

biphasic with low (Faslow) and high (Fashigh) populations present. The

Faslow population was relatively resistant to Fas-mediated apoptosis and

presumably represents the autoantibody secreting cells. One out of

11children born to mothers with SLE who were randamly selected in this study

had shown such a biphasic pattern with Faslow cells after anti-CD40

stimulation in vitro, and had detectable ANA. In addition, the prevalence of

allergic disease, especially atopic dermatitis and bronchial asthma, in the

children born to mothers with SLE was significantly higher than in controls.

(CONCLUSION)Our data suggest that genetic factors may influence the presence

not only of autoimmune disease but also allergic disease in children born to

mothers with SLE. Detection of immunological changes before the onset of SLE

by means of monitoring children born to mothers with SLE may be useful in

the elucidation of SLE pathogenesis.