Cytometry by time-of-flight immunophenotyping identifies a blood Sjögren's signature correlating with disease activity and glandular inflammation

BAFF overexpression increases lymphocytic infiltration in Sjögren's target tissue, but only inefficiently promotes ectopic B-cell differentiation

“…In agreement with the latter studies, we demonstrated here using both cell surface immunophenotyping and gene expression analyses that B cell differentiation did not progress beyond the follicular stage in lacrimal glands from NOD mice, with no signs of GC or plasma cell differentiation markers and gene expression during disease progression. This observation contrasts with what was reported in the glands from pSS patients which show GC formation in 10 to 30% of the cases and striking accumulation of plasma cells with a long-lived phenotype within the target tissue [3][4][5].…”

“…In combination with the observation that BAFF Tg mice also developed intense germinal center reactions with plasma cell accumulation in both spleen and lymph nodes [25], these results strongly suggest that increased BAFF levels observed in pSS patients could be responsible for ectopic B cell hyperactivation and GC formation in the exocrine tissue from these patients, an hypothesis which has been put forward oftentimes in the pSS field (reviewed in [27][28][29]). One should consider, however, that the disease phenotype observed in BAFF Tg mice differs significantly from human pSS, on multiple levels: (1) lymphocytic infiltrates in salivary glands from BAFF Tg mice mostly contain B cells with a marginal zone (MZ) phenotype and only very limited numbers of T cells [26]; (2) pSS-like manifestations in this model are only secondary to systemic hyperactivation and expansion of the B cell compartment in lymphoid organs whereas pSS patients show normal circulating numbers of B cells with the exception of memory B cells whose numbers are decreased [4]; (3) the pSS-like pathology in BAFF Tg mice is T-cell independent [30] and relies on the activation of MZ B cells [31]. For these reasons, it is currently unclear if these mechanisms apply and are relevant to more complex T-cell dependent autoimmune settings such as pSS.…”

“…Despite being the second most common rheumatic disease after rheumatoid arthritis, no disease-modifying drug is currently available to treat pSS patients. The histological hallmark of the disease is a multifocal nodular immune infiltration of the exocrine glands, predominantly composed of CD4 + T and B lymphocytes, but also CD8 + T cells and long-lived plasma cells [2][3][4]. In addition, ectopic germinal center (GC)-like structures were observed in 10 to 30% of patients [2,5]; their presence was associated with autoantibody seropositivity, disease activity, and higher risk of developing lymphoma [2,[5][6][7].…”

Standardisation of labial salivary gland histopathology in clinical trials in primary Sjögren's syndrome

“…[43][44][45][46][47] Imaging would not provide biological proof of mechanism however, or mechanistic understanding in the context of a failed study.…”

Clinical associations and expression pattern of the autoimmunity susceptibility factor DIORA-1 in patients with primary Sjögren’s syndrome

“…We observed no correlation with patient gender, age, salivary flow rate, extraglandular manifestations or adverse predictors of lymphoma (salivary gland enlargement, rheumatoid factor and lymphopenia) (data not shown). Interestingly, however, a recent study reported a blood plasmablast signature correlating with glandular inflammation in Ro/SSA +  patients with pSS 6. Limitations of the study relate to the fact that mechanistic studies were not performed and that additional patient groups were not investigated.…”