Newfound PsA Antibody Cross-Reacts With Skin, Entheses

January 29, 2015
Lois Wingerson

The first antibody found (researchers claim) to react with both skin and joints may explain why psoriasis can progress to psoriatic arthritis. Validated, it could also improve diagnosis.

Dolcino M, Lundardi C, Ottria A et al.Crossreactive Autoantibodies Directedagainst Cutaneous and Joint Antigens Are Present in Psoriatic Arthritis. PLoS One. 2014;Dec 16;9(12):e115424. doi: 10.1371/journal.pone.0115424

As a rheumatic disease diagnosed by exclusion based on clinical indicators,  psoriatic arthritis (PsA) is in dire need of an antibody of its own. These researchers from Italy declare that they have found one, with persuasive arguments: It reacts against antigens in both skin and entheses, and appears decisively specific.

They found the antibody by scouring the serum immunoglobulins (IgG) from100 patients with PsA (all Italian Caucasians, 64% male) at the University Hospital of Verona, looking for reactions to random peptides in a standard collection. They also tested serum from 50 age- and sex-matched healthy controls and 350 patients with a range of rheumatic diseases.

One protein, which they call the PsA peptide, triggered binding with IgG from  86% of PsA patients (and 84% of a separate validation panel of 70 different people with PsA). Only 1 of 30 patients who had psoriasis without arthropathy had antibodies against this peptide. There was no reaction whatever in sera from patients with systemic sclerosis, Sjôgren's syndrome, lupus, or ankylosing spondylitis (30 in each group).

The exception was rheumatoid arthritis (RA): Thirteen patients with seropositive RA (13%) and 3% with seronegative RA did recognize the antibody, so it is not completely discriminatory for PsA. But these authors point out that paired with rheumatoid factor and anti-citrullinated peptide antibodies (ACPA), the distinction is still possible.

The peptide also makes sense as a cross-reactive auto-antigen. Compared with human sequences in a US National Institutes of Health databank, it shares homology with the proteins fibrillin 3 (located in actin microfibrils in the skin), desmocollin 3 (found in epithelial cell junctions), and keratin 78, as well as a protein highly expressed in entheses, known as nebulin related anchoring protein or N-RAP.

Also shares homology with human interleukin 17B (IL17B) and with toll-like receptor 2 (TLR2), which plays an important role in recognizing microbes.

These cross-reactive antibodies sharing common epitopes "may be the missing link that explains the onset of enthesitis in patients with skin psoriasis," write the authors.

It also appears to answer a proposal that PsA is auto-inflammatory rather than autoimmune, based on the fact that no antigens common to the skin and the entheses had yet been identified in patients with the disease. Evidently PsA is indeed autoimmune.