Recent insights in the potential role of imaging modalities for diagnosing patients with primary Sjögren's syndrome

Within the last year, interesting developments regarding the assessment of salivary gland involvement in patients with clinical suspicion of, or diagnosed with primary Sjögren's syndrome (pSS) have been performed. In this review various topics will be discussed, starting with the use of salivary gland ultrasonography (SGUS) for the detection of glandular swelling. Furthermore, other imaging modalities, besides B-mode SGUS, which differentiate between pSS patients and healthy controls will be highlighted. Moreover, storage of ultrasonographic images and videos will be discussed briefly, as will be some potential biases and pitfalls. Finally, efforts that have been made to make incorporation of SGUS into the most recent classification criteria possible will be discussed, as well as the important steps that have been taken to develop a new semi-quantitative scoring system for the assessment of salivary gland involvement in patients with suspected or confirmed pSS

T cells in primary Sjögren's syndrome:targets for early intervention

A histologic hallmark of primary SS (pSS) is lymphocytic infiltration of the salivary and lacrimal glands, in particular by CD4+ T and B cells. In the early stages of the disease, infiltrates are dominated by CD4+ T cells, while B cell accumulation occurs at later stages. Activated T cells contribute to pathogenesis by producing pro-inflammatory cytokines and by inducing B cell activation, which results in the establishment of a positive feedback loop. In the inflamed glandular tissues, many different CD4+ effector subsets are present, including IFN-γ-producing Th1 cells, IL-17-producing Th17 cells and IL-21-producing T follicular helper cells. In blood from pSS patients, frequently observed abnormalities of the T cell compartment are CD4+ T cell lymphopenia and enrichment of circulating follicular helper T (Tfh) cells. Tfh cells are critical mediators of T cell-dependent B cell hyperactivity and these cells can be targeted by immunotherapy. Inhibition of T cell activation, preferably early in the disease process, can mitigate B cell activity and may be a promising treatment approach in this disease

Hydroxychloroquine Suppresses Interferon-inducible Genes and B Cell Activating Factor in Patients With Incomplete and New-onset Systemic Lupus Erythematosus

OBJECTIVE: Hydroxychloroquine (HCQ) is commonly used as first-line treatment for systemic lupus erythematosus (SLE). Interferon (IFN)-inducible gene expression, IFN-γ-induced protein 10 (IP-10) and B cell activating factor (BAFF) are early mediators in SLE. The purpose of this study was to analyze the effects of HCQ on these factors. METHODS: Patients with incomplete SLE (iSLE; antinuclear antibody titer ≥ 1:80, symptoms < 5 years, ≥ 1 objectified clinical American College of Rheumatology or SLE International Collaborating Clinics criteria), or new-onset, mild SLE were included when HCQ treatment was started for clinical reasons. Blood samples were taken at start and after 16 weeks. Three SLE-related IFN-inducible genes were measured in whole blood by real-time PCR, and an IFN score was calculated. Serum levels of IP-10 and BAFF were measured using ELISA. RESULTS: In total, 9 patients were included: 7 with iSLE and 2 with new-onset SLE. The median SLE Disease Activity Index (SLEDAI) was 4. After 16 weeks of treatment with HCQ, the expression of IFN-inducible genes decreased in 8 of 9 patients, and the IFN-3 score decreased significantly (P = 0.012). There was a trend towards lower IP-10 levels (P = 0.055), and a significant decrease in BAFF levels (P = 0.023). CONCLUSION: HCQ suppresses IFN score and BAFF levels in patients with iSLE or new-onset SLE, and there is a trend towards lowering IP-10 levels. As these biomarkers are early mediators in SLE, this might support the hypothesis that HCQ could influence disease progression. However, prospective research with a larger sample size and longer follow-up is needed

From incomplete to complete systemic lupus erythematosus; A review of the predictive serological immune markers

Systemic lupus erythematosus (SLE) is a complex and heterogeneous autoimmune disease. A main challenge faced by clinicians is early identification of SLE, frequently resulting in diagnostic delay. Timely treatment, however, is important to limit disease progression, and prevent organ damage and mortality. Often, patients present with clinical symptoms and immunologic abnormalities suggestive of SLE, while not meeting classification criteria yet. This is referred to as incomplete SLE (iSLE). However, not all these patients will develop SLE. Therefore, there is need for predictive biomarkers that can distinguish patients at high risk of developing SLE, in order to allow early treatment. This article reviews the current literature on immunological changes in patients with stages preceding SLE, focusing on autoantibodies, type-I and -II interferons, and the complement system. We also provide an overview of possible predictive markers for progression to SLE that are applicable in daily clinical practice