Disturbed B Cell Homeostasis in Newly Diagnosed Giant Cell Arteritis and Polymyalgia Rheumatica

Abstract

Objective. Several lines of evidence indicate that B cells may be involved in the immunopathology of giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). This study was undertaken to examine the distribution of defined B cell subsets, including effector B (Beff) cells and regulatory B (Breg) cells, in patients with GCA and patients with PMR before and after corticosteroid treatment.Methods. Circulating B cells were analyzed in 34 newly diagnosed, untreated patients with GCA or PMR, and in 44 followup samples from patients with GCA or PMR who received corticosteroids for 2 weeks or 3 months. For comparison, 40 age-matched healthy controls and 11 rheumatoid arthritis (RA) patients were included. Serum BAFF levels were determined, and temporal arteries were studied by immunohistochemistry.Results Conclusion. We show for the first time that the distribution of B cells is highly disturbed in GCA and PMR and that B cells likely contribute to the enhanced IL-6 response in both diseases.

New insights into the pathogenesis of giant cell arteritis

“…B cell numbers recover rapidly in treated patients with GCA and PMR in remission and the B cell numbers are inversely correlated with ESR, C-reactive protein levels, and serum BAFF levels [89]. Although the role of B cells has been explicitly neglected by some investigators [10,86,91,92] their presence in GCA arterial lesions has been previously and repeatedly recognized by other investigators [84,85,93,94]. Further supporting the role of B cells in the pathogenesis of GCA is the demonstration that the presence of B cells, in a significant proportion of GCA arteries, is invariably associated with a defined T cell/B cell segregation surrounding a central area consisting of CD21 + cells (FDC) and with the significant over-expression of chemokines enhancing B-cell survival and expansion such as BAFF, APRIL and CXCL13 [57].…”

Pathogenesis of polymyalgia rheumatica

“…B-lymphocytes are crucial components of both innate and adaptive immunity. Although an autoimmune component has been never demonstrated in PMR patients, a decreased frequency of circulating B cell has been demonstrated in PMR, rapidly recovered after steroid treatment (57). Interestingly, in PMR the B cell numbers are inversely correlated with erythrocyte sedimentation rates, C-reactive protein levels, and serum BAFF levels.…”

“…Interestingly, in PMR the B cell numbers are inversely correlated with erythrocyte sedimentation rates, C-reactive protein levels, and serum BAFF levels. In particular, the frequency of Tumour necrosis factor α-positive Beff cells was decreased in patients newly diagnosed with PMR and normalized by steroid treatment (57). More recently, it has been demonstrated that B-cell lymphopenia and abnormal Bcell subset distribution, associated with disease activity and IL-6 concentration, are corrected by the IL-6 antagonist tocilizumab (57).…”

Utility of serological biomarkers for giant cell arteritis in a large cohort of treatment-naïve patients

“…The number of patients diagnosed with GCA by 2050 is projected to be over 3 million in Europe, North America, and Oceania, representing a significant clinical and financial challenge [8]. Several previous reports have described potential serological markers for GCA [9][10][11][12][13][14][15][16][17][18], among them cytokines, chemokines, growth factors, cell adhesion molecules, and matrix metalloproteinases (MMPs). In 2000, Weyand et al emphasized that interleukin (IL)-6 may act as a biological marker of GCA activity in untreated and treated GCA patients [19].…”