Immunologic dysfunction in scleroderma: evidence for increased mast cell releasability and hla–dr positivity in the dermis

Abstract

To investigate the role of mast cells and cellmediated immunity in the pathogenesis of scleroderma, we studied wheal size after skin testing with compound 48/80, a liberator of mast cell histamine, and demonstrated increased mast cell releasability in skin that appeared normal, adjacent to involved skin. Immunofluorescent staining for HLA-DR showed dermal positivity in 12 of 13 involved-and 9 of 13 uninvolved-skin biopsy specimens from scleroderma patients, compared with only 1 of 10 controls. By immunoperoxidase staining, most of the DR positivity was found in fibroblastlike cells. These findings further support the notion of immunologic dysfunction in scleroderma.Systemic sclerosis (SSc) is a multisystem disease characterized by varying degrees of proliferative changes in small arteries and arterioles, obliterative microvascular lesions, and fibrosis in the skin and internal organs. Although the etiology of the disease is unclear, there is evidence that immunologic mechanisms may be important in its pathogenesis. The

Mast cell/fibroblast interactions

“…Several studies give evidence suggesting MC contribution to the pathogenesis of fibrotic skin diseases such as scleroderma, cGVHD or eosinophilic fasciitis [23][24][25][26].…”

Mast cells exert pro-inflammatory effects of relevance to the pathophyisology of tendinopathy

“…The primary cell type in tendons, tenocytes, may be influenced by the presence of mast cells in their microenvironment. Although associations between mast cells and a number of chronic conditions including pulmonary fibrosis [1], renal fibrosis [2], and scleroderma [3] have been established, very few data are available on the possible link between mast cells and the failed tissue healing or fibrosis that is evident in chronically injured tendon tissues. We have previously documented a greater number of mast cells in the tendons of patellar tendinopathy subjects compared with healthy controls [4], and increased mast cell numbers have also been detected in the injured rotator cuff [5].…”

Bilateral Bronchoalveolar Lavage in Progressive Systemic Sclerosis: Interlobar Variability, Lymphocyte Subpopulations, and Functional Correlations

“…Amento and Hayes [21] have reported that T lympho cytes may modulate the synthesis/destruction balance of the extracellular matrix by the production of in terferon gamma which inhibits collagen synthesis and the release of lymphotoxin, the action of which is to stimulate the collagen synthesis by synovial fibro blasts. An alternative hypothesis is that lymphocytes may contribute to fibroblastic activation, but may leave the fibrotic areas at a later stage of involvement, as suggested in a study on skin byopsies by Pearson et al [22], The value of the lymphocyte/granulocyte ratio as an independent marker of functional derangement needs to be confirmed in larger studies.…”