P7.83 A TH₁ - ASSOCIATED ANTI-HAIR FOLLICLE IgG₁ ANTIBODY RESPONSE PREDOMINATES IN HUMAN ALOPECIA AREATA

ML O’Shea, L Mooney, ¹ J-C Bystryn, DJ Tobin.

Dept. of Biomedical Sciences, Uni. of Bradford, Bradford, England; Dept. of Dermatology, NYU Medical School, New York, USA

Alopecia areata (AA) is a hair follicle (HF) disorder that targets the growing (anagen) HF featuring both anti-HF-specific autoantibodies and autoreactive T cells, though T cells the likely to be the principal effector cells in the pathogenesis of this diease of unknown etiology. The characteristic perifollicular immune cell infiltrate in acute AA contains principally T cells, but also antigen presenting cells like B cells (and plasma cells), macrophages and Langerhans cells. Patient sera contain circulating high-titer antibodies to antigens that are preferentially expressed by anagen HF and are mainly of the IgG isotype. By contrast, low-titer “natural antibodies“ in normal individiuals are typically IgM. There is growing evidence however, that autoimmune diseases can exhibit preferred IgG subclass usage, with important functional implications in terms of complement activation, neutralization, opsinisation and sensitization for killing by NK cells. It is not known whether AA also has preferred IgG subclass usage. Here, we evaluate the specific IgG subclass usage in this presumptive autoimmune disease.

While all AA patients exhibited some IgG and IgM anti-HF antibody reactivity, 40% of the highest titer reactivities were IgG while only <10% were IgM. These high-titer antibodies were directed to 38-60 kDa HF antigens, confirming previous reports. The frequencies of anti-HF IgG antibody subclass usage was IgG₁ (60% of patients), followed by IgG₃ (33% of patients), IgG₂ (5%) and IgG₄ (0%). A single patient exhibited both IgG₁ and IgG₃ antibodies.

These results suggest that antibody affinity maturation in AA, as in other autoimmune diseases [eg. prediabetes, rheumatoid arthritis, tyroiditis] is biased to IgG₁ – an IgG subclass with marked neutralizing, opsonizing and complement-activating functions. In this way, these results further support a Th₁-dependent immune response to HF antigens in AA, and so resemble other organ-specific autoimmune diseases and inflammatory reactions.