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

Personalizing psychological care for chronic cancer-related fatigue:A case study on symptom dynamics

Approximately 25% of cancer patients suffer from chronic cancer-related fatigue (CCRF), which is a complex, multifactorial condition. While there are evidence-based interventions, it remains unclear what treatment works best for the individual patient. Psychological network models can offer a schematic representation of interrelations among fatigue and protective and perpetuating factors for the individual patient. We explored whether feedback based on these individual fatigue networks can help personalize psychological care for CCRF. A 34-year old woman with CCRF was referred to our mental healthcare institute for psycho-oncology. During the waitlist period, she filled out an experience sampling app for 101 days, including five daily assessments of fatigue, pain, mood, activity and fatigue coping. The interplay between items was visualized in network graphs at the moment-level and day-level, which were discussed with the patient. For example, acceptance of fatigue in the past three hours was associated with less hopelessness and less fatigue in the following moment. At the day-level, acceptance was also being associated with less fatigue, less hopelessness, a better mood, and more motivation to do things. The patient recognized these patterns and explained how unexpected waves of fatigue can make her feel hopeless. This started a dialogue on how cultivating acceptance could potentially help her handle the fatigue. The patient would discuss this with her therapist. Feedback based on individual fatigue networks can provide direct insight into how one copes with CCRF and subsequently offer directions for treatment. Further research is needed in order to implement this in clinical practice

Variation at the capsule locus, cps, of mistyped and non-typable Streptococcus pneumoniae isolates

The capsule polysaccharide locus (cps) is the site of the capsule biosynthesis gene cluster in encapsulated Streptococcus pneumoniae. A set of pneumococcal samples and non-pneumococcal streptococci from Denmark, the Gambia, the Netherlands, Thailand, the UK and the USA were sequenced at the cps locus to elucidate serologically mistyped or non-typable isolates. We identified a novel serotype 33B/33C mosaic capsule cluster and previously unseen serotype 22F capsule genes, disrupted and deleted cps clusters, the presence of aliB and nspA genes that are unrelated to capsule production, and similar genes in the non-pneumococcal samples. These data provide greater understanding of diversity at a locus which is crucial to the antigenic diversity of the pathogen and current vaccine strategies

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