Increased circulating anti‐α6‐integrin autoantibodies in psoriasis and psoriatic arthritis but not in rheumatoid arthritis

Abstract

In psoriatic skin, laminin integrity is altered, which could lead to insufficient laminin integrin interactions, leaving the α6-integrin exposed and possibly accessible for autoantibody production. Therefore we investigated the presence of anti-α6-integrin autoantibodies in the serum of patients with psoriasis vulgaris (Ps), psoriatic arthritis (PsA) and rheumatoid arthritis (RA) in comparison with healthy donors. The level of circulating anti-α6-integrin antibodies was determined by enzyme-linked immunoassay using α6-integrin fragments. Antibodies against at least one recombinant fragment were found in approximately 30% of Ps and PsA patients. In contrast, in RA patients, the frequency of antibodies was similar to healthy controls. Our study shows the presence of anti-α6-integrin antibodies in Ps and PsA but not in RA, which could indicate ongoing abnormal processes in the skin. Anti-α6-integrin autoantibodies may contribute to the formation of micro-wounds in the skin and to the characteristic wound-healing phenotype in psoriasis.

Could basement membrane alterations, resembling micro‐wounds at the dermo‐epidermal junction in psoriatic non‐lesional skin, make the skin susceptible to lesion formation?

“…Data indicate that protein complexes that are formed when cells are under stress could possess immunological features that can modulate the host's immune response and induce autoantibody production. In the psoriatic non‐lesional tissue, abnormal BM proteins may expose novel epitopes to immune cells and this, together with other immune activating factors, can induce autoantibody formation 84 . It is presently not completely understood how much autoimmunity contributes to psoriasis, and although no particular autoantibody could be linked to the disease so far, one cannot rule out the possibility that autoantibodies may participate in the maintenance of chronic inflammation.…”

Interaction of Psoriasis and Bullous Diseases

“…Occasional production of autoantibodies against BP180 and desmogleins in lichen planus cases has been reported regardless of accompanying blister formation, probably because of the consequence of interface dermatitis, suggesting Th1/Th2 dichotomy among lichen planus vs. pemphigus or pemphigoid diseases ( 150 ). In psoriasis, however, production of neither autoantibodies against BP180 nor desmogleins, but α6 integrin ( 151 ), in psoriasis has been reported without complication with blistering diseases. It is therefore unlikely that psoriasis and bullous pemphigoid or pemphigus diseases are sharing their primary effector memory T cells.…”

Current knowledge on autoantigens and autoantibodies in psoriasis

“…In 2014, cathelicidin (LL‐37) was the first autoantigen to be identified 11 and more followed rapidly in the following years (disintegrin‐like and metalloprotease domain containing thrombospondin type 1 motif‐like 5 (ADAMTSL5), phospholipase A2 group IVD (PLA2G4D), keratin 17 and heterogeneous nuclear ribonucleoprotein A1 (hnRNP‐A1) as a potential autoantigen) 9,11‐13 . Furthermore, while the role of autoreactive T cells is becoming increasingly evident, only recently autoantibodies have been observed in patients with psoriasis and PsA, including antinuclear antibodies (ANA), antibodies that bind to the antimicrobial peptide LL‐37, small nuclear RNP and cytoplasmic RNP and integrins 14‐17 . However, the exact role of these autoantibodies in the pathogenesis of psoriasis and PsA remains to be illuminated as well as the pathways through which they might be generated, for example activation of autoreactive B cells through neutrophil extracellular traps (NET).…”