A Review on the Potential Role of Basement Membrane Laminin in the Pathogenesis of Psoriasis

Abstract

We have previously reviewed alterations to basement membrane laminin in psoriasis and how disruption of this layer could lead to at least some of the pathological changes observed. We here postulate that basement membrane laminin is the key antigen in driving psoriasis, inducing a T cell-mediated autoimmune response. For laminin to be considered as the key autoantigen in psoriasis, it would be reasonable to expect the following to be demonstrable: (1) that autoantigens are present in psoriatic inflammation; (2) that basement membrane laminin is perturbed in involved and uninvolved skin, and that some of the pathological changes associated with psoriasis could be predicted as a sequel to this; (3) that disruption of the basement membrane is among the earliest events in the evolution of psoriatic lesions; (4) that as streptococcal pharyngitis is the most clearly defined event to trigger or exacerbate psoriasis, then a T cell-mediated autoimmune response to laminin should be anticipated as a potential sequelae to streptococcal pharyngitis; (5) that T cells in psoriasis can be shown to react to peptides with homology to laminin; (6) that HLACw6, as the most closely related gene associated with psoriasis and which is involved in antigen expression, should be preferentially expressed within lesional psoriasis towards the basement membrane, together with other proximal associated immune activity; and (7) that there is some association between antilaminin pemphigoid, a humorally mediated autoimmune disease to skin basement membrane laminin, and psoriasis. We here review the data relevant to each of these requirements.

Regulation of the Immune System by Laminins

“…Peripheral human CD4 + and CD8 + T-cell clones isolated from a rheumatic carditis patient show reactivity against laminin [99]. Laminin might also be key autoantigens in psoriasis, inducing a T-cell-mediated autoimmune response [100]. The relationship of laminins to autoimmunity may be a consequence of their ubiquitous presence and interaction with many components of the immune system.…”

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

“…This finding suggests a potential antigen localized at the DEJ playing a role in the initiation of the disease. In addition, it has been shown that the disruption of basement membrane is specific for psoriasis compared with other common inflammatory diseases …”

Autoimmunity to heterogeneous nuclear ribonucleoprotein A1 in psoriatic patients and correlation with disease severity

“…Über pathogene Mechanismen, die immunvermittelt sind, ist in jüngerer Zeit einiges bekannt geworden, sie werden jedoch noch immer nicht völlig verstanden und insbesondere zu den Ursachen der Psoriasis sind die Erkenntnisse bislang begrenzt. Angesichts der möglichen autoimmunen Natur der Erkrankung, haben zahlreiche Autoren versucht, die beteiligten Autoantigene zu fi nden [5][6][7][8][9][10][11][12][13][14][15][16][17] . Mehrere Moleküle wurden identifi ziert oder vorgeschlagen, aber bei den meisten dieser Antigene beschränkt sich verfügbare Evidenz auf eine einzige Publikation [5][6][7][8][9][10][11][12][13][14][15][16][17] .…”

“…Immune‐mediated pathogenic mechanisms have become clearer recently, but they are not yet completely understood and knowledge of the causes of psoriasis is rather scarce. In view of the possible autoimmune nature of the disease, many authors have attempted to identify the autoantigen(s) involved . Several molecules have been identified or postulated, but for most of them, the available evidence is limited to a single paper .…”