Interstitial lung disease in scleroderma. Immune complexes in sera and bronchoalveolar lavage fluid

Abstract

Interstitial lung disease is a common feature of scleroderma (systemic sclerosis), and it may be a major determinant of morbidity and mortality. Analysis of bronchoalveolar lavage fluid from patients with scleroderma has shown evidence of inflammation in the lower respiratory tract of many patients. We have analyzed sera and bronchoalveolar lavage fluid from scleroderma patients for the presence of immune complexes, which may play a role in the inflammatory process. Using a solid-phase C1q enzyme-linked immunosorbent assay, we detected immune complexes in the sera of 6 of 23 patients (26%) and in none of 32 controls (P less than 0.01). All 6 patients with serum immune complexes had inflammatory cells in bronchoalveolar lavage fluid, and the presence of serum immune complexes correlated with the percentage of neutrophils in lavage fluid (P less than 0.02). Immune complexes were detected in lavage fluid of 11 of 21 patients (52%) compared with 1 of 7 normal controls (14%). Subjects having immune complexes in lavage fluid had a lower forced vital capacity than did those without lavage fluid immune complexes (P less than 0.05). The levels of immune complexes in bronchoalveolar lavage fluid exceeded those in serum by a mean of 45-fold, suggesting either local formation or selective deposition of immune complexes in the lower respiratory tract of some scleroderma patients.

Interstitial Lung Disease of Systemic Sclerosis

“…Similar findings have been reported in IPF patients [24], where IgG-secreting cells are present in BAL fluid [25]. Using a Clq binding assay, SSc BAL fluid has been shown to contain higher concentrations of immune complexes compared to serum, suggesting immunologic activation within the lower respiratory tract [26,27]. Similar results have been obtained in studies of patients with IPF, and it has been theorized that immune complexes stimulate alveolar macrophages and other cells to release chemotdctic factors, proteolytic enzymes and oxygen radicals [28].…”

Osteopontin Links Myeloid Activation and Disease Progression in Systemic Sclerosis

“…Indeed, numerous studies have documented the presence of immune complexes (ICs) in sera, lungs, and bronchoalveolar lavage (BAL) fluid of SSc patients, potentially implicating them in the pathogenesis. [12][13][14][15] Monocyte/macrophage activation has been observed in fibrotic SSc skin and lung tissue. [16][17][18] Although the upstream activators remain unknown, it is plausible that ICs are among the key triggers of activating myeloid cells and sustaining the chronic inflammation and fibrosis in SSc tissue.…”

Inflammation and Pulmonary Fibrosis

“…In addition, intense expression of PDGF by the endothelial lining of small capillaries in scleroderma (Gay et al, 1989) suggests that endothelin may act in synergy with other cytokines and growth factors to activate fibroblasts. Consistent with the concept that immune processes initiate inflammation, immune complexes are found in the epithelial lining fluid of patients with scleroderma (Jansen et al, 1984;Silver et al, 1986). Several lines of evidence support the concept that alveolitis, i.e.…”