Juvenile onset Systemic Lupus Erythematosus thyroid dysfunction: a subgroup with mild disease?

The aim of this study was to evaluate the frequency of thyroid dysfunction and thyroid antibodies in patients with juvenile onset Systemic Lupus Erythematosus (JOSLE) and its association with clinical and immunological features. Seventy-seven patients with JOSLE, 64 females, median age 19 years, were consecutively enrolled from March to December 2007. Clinical data related to thyroid dysfunction and lupus were obtained by chart review and patient interview. Serum levels of TSH, free T4, anti-thyroglobulin (TgAb), anti-thyroperoxidase (TPOAb), TRAb and lupus related autoantibodies were analyzed by standard techniques. Nine patients were diagnosed as hypothyroidism and 4 hyperthyroidism. 28% JOSLE patients had moderate/high titer of thyroid antibodies: 23% TgAb, 2.6% TPOAb and 3.9% TRAb. JOSLE patients with positive thyroid autoantibodies had higher frequency of anti-U1RNP antibodies than patients without these antibodies (40.9 vs. 14.5%, OR:0.25, CI:0.08-0.76, p = 0.017). Furthermore, renal/neurological/hematological involvement was less frequently observed in patients with hypothyroidism (55.6 vs. 87.5%, OR:0.18, CI:0.04-0.81, p = 0.035) and with thyroid antibodies (68.4 vs. 90.9%, OR:0.22, CI:0.06-0.82, p = 0.027) than in patients without these alterations. No association with PTPN22 polymorphism was found. In conclusion, JOSLE patients have high prevalence of subclinical hypothyroidism. The novel association of anti-thyroid antibodies with anti-U1RNP antibodies in JOSLE seems to identify a subgroup of patients with less life-threatening organ involvement.

The penetration of autoantibodies into cells may induce tolerance to self by apoptosis of autoreactive lymphocytes and cause autoimmune disease by dysregulation and/or cell damage.

Autoantibodies to intracellular constituents often occur naturally. This would be difficult to understand were they unable to penetrate live cells, as was once generally accepted; however, they can and in so doing may alter cell functions, cause damage and even kill cells by apoptosis. Different autoantibodies have different effects and in this paper, further to our previous report on the penetration of anti-DNA, the penetration of anti-RNP, which may be a possible cause of apoptosis, is demonstrated. Penetration of lymphocytes by autoantibodies may play a role in the causation of autoimmune disease, influencing immune regulation and causing cell damage either directly or through nucleosomal DNA release as a result of apoptosis. This, in turn, could also further promote antigen-driven production of anti-DNA. In addition, by causing apoptosis of autoreactive cell clones, natural autoantibodies could influence tolerance during development and also later in life, thus, paradoxically, helping prevent autoimmune disease.