Association Between Minor Salivary Gland Biopsy During Sjӧgren’s Syndrome and Serologic Biomarkers: A Systematic Review and Meta-Analysis

Abstract

ObjectivePatients with primary Sjögren’s syndrome (pSS) may develop a potentially severe disease with extra-glandular involvement and lymphoma insurgence. Minor salivary gland biopsy is routinely used in the disease diagnosis, but its potential role as a biomarker for clinical disease presentation and prognosis is still poorly understood.MethodsWe performed a systematic review and meta-analysis on clinical presentation and prognosis in pSS patients who underwent minor salivary gland biopsy at diagnosis according to the PRISMA guidelines.ResultsWe included five retrospective studies and 589 pSS patients. Ectopic GCs presence was not associated with a significant increase in the odds ratio for the clinical variables explored such as salivary gland swelling, arthritis, and Raynaud’s phenomenon. As far as serological features are concerned, ectopic GCs presence accounted for an increased ratio of antibodies anti-SSA (OR = 3.13, 95% CI: 1.25–7.85, p = 0.02, I2 = 79%), anti-SSB (OR = 3.94, 95% CI: 1.50–10.37, p = 0.0005, I2 = 80%), and RFs presence (OR = 3.12, 95% CI: 1.94–5.00, p < 0.00001, I2 = 0%).ConclusionsThis study showed that the association between ectopic GC in salivary glands identifies a clinical subset characterized by autoantibodies presence, and probably pSS patients affected from a more severe disease.

High-throughput sequencing of IgH gene in minor salivary glands from Sjögren's syndrome patients reveals dynamic B cell recirculation between ectopic lymphoid structures

“…In addition to VH1-69, among highly proliferating and hypermutated shared clonotypes recirculating in different SG we frequently observed other VDJ rearrangements, such as VH4-34, used by inherently autoreactive B cells (43), supporting the evidence that ELS in SS patients are unable to exert the control mechanisms of follicular exclusion of autoreactive B cells allowing their entrance in ectopic GC and their local differentiation in autoantibody producing cells (44) resulting in the accumulation of anti-Ro/SSA anti-La/SSB reactive perifollicular plasma cells (8,45). The well described association between ELS and circulating autoantibodies reported in several studies in SS (46,47) further suggest that local autoantibody production in the SG is reflected, at least partially, in the peripheral compartment.…”

Interstitial Lung Disease and Pulmonary Damage in Primary Sjögren’s Syndrome: A Systematic Review and Meta-Analysis

“…We did not find any association between the serologic status in terms of autoantibodies presence and the ILD prevalence. We know that anti-Ro/SSA antibodies have a pivotal role in pSS classification and mirror what happens in the salivary glands, and their presence is associated with early diagnoses, parotidomegaly, and sicca symptoms [ 58 , 59 , 60 ]. Data regarding the association between anti-Ro/SSA antibodies presence and pSS-ILD are controversial, and their relation should be clarified [ 32 , 61 , 62 ].…”

“…These differences partially explain the large variability observed in the results. On the other hand, ILD is now considered one of the most common and severe morbidities in many immunologic diseases, both autoimmune and autoinflammatory, sometimes being the main cause of death in these patients [ 58 , 59 , 60 , 63 , 64 , 65 ]. More data are needed to better explore ILD prevalence, and to clarify whether the observed differences may be related to the studies’ characteristics.…”

Minor Salivary Gland Surgery and Histopathological Scoring System: A Systematic Review

“…Although it is not employed at the same level as the other two systems, it has been used in some studies to predict the risk of lymphoma and to assess the prevalence of SS [40]. e prognostic role of MSGB in SS is given by the presence of ectopic germinal centers (GCs) as they contribute to determine the degree of B-cell proliferation and maturation, the generation of somatic hypermutations, and the development of class-switch recombinations [41]. Immune cell infiltration greater degree and ectopic GCs greater number are associated with anti-SSA/B autoantibodies higher prevalence, increased disease severity, extraglandular manifestations, and the onset of MALT lymphoma [42].…”

“…Comini et al[28] Syed et al[29] Friedman et al[30] Tarpley et al[31] Costa et al[32] Chen et al[33] Daniels et al[34] Barone et al[35] Han et al[36] Kapsogeorgou et al[37] Rooper et al[38] Carubbi et al[39] Fragkioudaki et al[40] Berardicurti et al[41] Stergiou et al[42] …”