Invariant NKT cells and rheumatic disease: Focus on primary sjogren syndrome

Primary Sjogren syndrome (pSS) is a complex autoimmune disease mainly affecting salivary and lacrimal glands. Several factors contribute to pSS pathogenesis; in particular, innate immunity seems to play a key role in disease etiology. Invariant natural killer (NK) T cells (iNKT) are a T-cell subset able to recognize glycolipid antigens. Their function remains unclear, but studies have pointed out their ability to modulate the immune system through the promotion of specific cytokine milieu. In this review, we discussed the possible role of iNKT in pSS development, as well as their implications as future markers of disease activity

CD4 T lymphocyte autophagy is upregulated in the salivary glands of primary Sjögren’s syndrome patients and correlates with focus score and disease activity

Background: Primary Sjögren’s syndrome (pSS) is a common chronic autoimmune disease characterized by lymphocytic infiltration of exocrine glands and peripheral lymphocyte perturbation. In the current study, we aimed to investigate the possible pathogenic implication of autophagy in T lymphocytes in patients with pSS. Methods: Thirty consecutive pSS patients were recruited together with 20 patients affected by sicca syndrome a nd/or chronic sialoadenitis and 30 healthy controls. Disease activity and damage were evaluated according to SS disease activity index, EULAR SS disease activity index, and SS disease damage index. T lymphocytes were analyzed for the expression of autophagy-specific markers by biochemical, molecular, and histological assays in peripheral blood and labial gland biopsies. Serum interleukin (IL)-23 and IL-21 levels were quantified by enzyme-linked immunosorbent assay. Results: Our study provides evidence for the first time that autophagy is upregulated in CD4+ T lymphocyte salivary glands from pSS patients. Furthermore, a statistically significant correlation was detected between lymphocyte autophagy levels, disease activity, and damage indexes. We also found a positive correlation between autophagy enhancement and the increased salivary gland expression of IL-21 and IL-23, providing a further link between innate and adaptive immune responses in pSS. Conclusions: These findings suggest that CD4+ T lymphocyte autophagy could play a key role in pSS pathogenesis. Additionally, our data highlight the potential exploitation of T cell autophagy as a biomarker of disease activity and provide new ground to verify the therapeutic implications of autophagy as an innovative drug target in pSS

Short-Facelift Approach in Temporal Artery Biopsy: Is It Safe?

Giant cell arteritis (GCA) is a quite common panarteritis of the elderly that affects medium- and large-size arteries. Despite the increasing role of imaging with advancing technology, the gold standard for the diagnosis of GCA is still the temporal artery biopsy. A described complication of superficial temporal artery biopsy (STAB), for which incidence is not clear, is the accidental damage of the frontal branch of the facial nerve. In this paper, we described the short-scar facelift surgical approach for STAB on 23 consecutive patients who underwent unilateral superficial temporal artery biopsy for GCA suspicion. We collected data in terms of postoperative complications, biopsy specimen length, biopsy result and cosmetic appearance of the scar. In our experience, this surgical approach combines the advantage of avoiding incisions within the dangerous anatomical area, minimizing the risk of facial nerve damage, with an acceptable complication rate and a good final aesthetic result which avoids visible scarring

Adult-onset Still's disease: Evaluation of prognostic tools and validation of the systemic score by analysis of 100 cases from three centers

Background: Adult-onset Still's disease (AOSD) is rare inflammatory disease of unknown etiology that usually affects young adults. The more common clinical manifestations are spiking fevers, arthritis, evanescent rash, elevated liver enzymes, lymphadenopathy, hepatosplenomegaly, and serositis. The multi-visceral involvement of the disease and the different complications, such as macrophage activation syndrome, may strongly decrease the life expectancy of AOSD patients. Methods: This study aimed to identify the positive and negative features correlated with the outcome of patients. A retrospective analysis of AOSD patients prospectively admitted to three rheumatologic centers was performed to identify the clinical features present at the time of diagnosis and to predict the possible outcome. Furthermore, we investigated the as yet to be validated prognostic value of the systemic score previously proposed. Results: One hundred consecutive AOSD patients were enrolled. The mean systemic score showed that the majority of patients had a multi-organ involvement. Sixteen patients showed different complications, mainly the macrophage activation syndrome. A strong increase of inflammatory markers was observed. All patients received steroids at different dosages, 55 patients in association with immunosuppressive drugs and 32 in association with biologic agents. Sixteen patients died during the follow-up. Regression analysis showed that the higher values of the systemic score and the presence of AOSD-related complications, assessed at the time of diagnosis, were significantly correlated with patient mortality. A prognostic impact of the systemic score of 65 7.0 was reported. Conclusions: Our study showed that a higher systemic score and the presence of AOSD-related complications at the time of diagnosis were significantly associated with mortality. Of note, a cut-off at 7.0 of the systemic score showed a strong prognostic impact in identifying patients at risk of AOSD-related death

Successful intravenous immunoglobulin treatment for steroid-resistant eosinophilic enteritis in a patient with systemic lupus erythematosus.

Eosinophilic gastroenteritis is a rare condition of unknown etiology characterized by eosinophilic infiltration of the bowel. Corticosteroids are the mainstay of EG therapy. Although rare, steroid-resistant EG could be a life-threatening condition with tissue destructive evolution. Associations of eosinophilic gastroenteritis with systemic lupus erythematosus have rarely been reported. In this report we describe a case of successful IVIG treatment in a patient with systemic lupus erythematosus and steroid-refractory eosinophilic gastroenteritis

A 2-year comparative open label randomized study of efficacy and safety of etanercept and infliximab in patients with ankylosing spondylitis

The signs and symptoms of ankylosing spondylitis (AS) respond inadequately to nonsteroidal antiinflammatory drugs, corticosteroids, and disease modifying antirheumatic drugs in quite a number of patients. Tumor necrosis factor inhibitors have demonstrated to be of value in reducing AS disease activity in clinical trials. The efficacy and safety of both etanercept and infliximab in patients with ankylosing spondylitis were compared in a 2-year open label randomised study. Our results are consistent with a significant more rapid clinical improvement in the infliximab treated group. Treatment with both etanercept and infliximab at the end of the study was effective, safe, and well tolerated. \ua9 2009 Springer-Verlag

Adalimumab efficacy in enteropathic spondyloarthritis: A 12-mo observational multidisciplinary study

AIM To report adalimumab (Ada) efficacy on articulargastrointestinal disease and health-related quality of life (HRQoL) in patients with enteropathic spondyloarthritis (ES). METHODS A cohort of 52 patients with ES was evaluated in the departments of gastroenterology and internal medicine. At baseline, all patients underwent assessment by an integrated gastro-rheumatologic evaluation of articular and gastrointestinal activity, as well patient reported outcomes (PROs) of the HRQoL questionnaires. After this integrated evaluation and following a specific working flowchart, the Ada anti-tumor necrosis factor (TNF)-inhibitor was assigned to a cohort of 30 patients and its clinical efficacy was evaluated at baseline and after 6-mo and 12-mo treatment by the following tests: (1) Ankylosing Spondylitis Disease Activity Score- C-Reactive Protein (ASDAS-CRP); Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Metrology Index (BASMI) for articular activity; (2) Inflammatory Bowel Disease Questionnaire (IBDQ), Crohn's Disease Activity Index (CDAI) and partial Mayo (pMayo) score for gastrointestinal symptoms and activity; and (3) Health Assessment Questionnaire (HAQ), Patient Global Assessment (PGA) and Short Form-36 health survey (SF-36) questionnaires for PROs of the HRQoL. RESULTS Integrated evaluation and management of the patients affected by ES, carried out simultaneously by a gastroenterologist and a rheumatologist, allowed clinicians to choose the optimal therapeutic strategy. In a cohort of 30 ES patients affected by active articular and gastrointestinal disease, or axial active articular inflammation, Ada led to fast and sustained improvement of both articular and gastrointestinal disease activities. In fact, all the clinimetric evaluation tests exploring articular or gastrointestinal activity, as well as all the HRQoL scores, showed a significant improvement having been achieved at the earliest (6-mo) assessment. This important clinical improvement was maintained at the 12-mo follow-up. Importantly, global and gastrointestinal quality of life significantly correlated with articular disease activity, providing evidence to support that the integrated evaluation is the best option to manage patients with ES. CONCLUSION Ada treatment, upon multidisciplinary (gastrorheumatologic) evaluation, significantly improves both articular and gastrointestinal inflammation, thereby improving the HRQoL in patients affected by ES

IL-17 polarization of MAIT cells is derived from the activation of two different pathways

MAIT cells are expanded in salivary glands of patients with Sjogren's syndrome and are IL-17 polarized. IL-7 and IL-23 induce IL-17 production activating two different pathways: IL-7 stimulation induces in fact a significant STAT3 and HIF1alpha upregulation, conversely, IL-23 stimulation significantly induces RORc overexpression in MAIT cells of patients with Sjogren's syndrome

Concomitant MPZ and MFN2 Gene Variants and Charcot Marie Tooth Disease in a Boy: Clinical and Genetic Analysis-Literature Review

: Charcot- Marie- Tooth (CMT) disease includes a group of clinically and genetically heterogeneous neuropathic disorders with an estimated frequency of 1 on 2.500 individuals. CMTs are differently classified according to the age of onset, type of inheritance, and type of inheritance plus clinical features. For these disorders, more than 100 genes have been implicated as causal factors, with mutations in the PMP22 being one of the most common. The demyelinating type (CMT1) affects more than 30% of the CMTs patients and manifests with motor and sensory dysfunctions of the peripheral nervous system mainly starting with slow progressive weakness of the lower extremities. We report here a 12 year- old boy presenting with typical features of CMT1 type, hearing impairment, and inguinal hernia who at the next-generation sequence analysis displayed a concomitant presence of two variants: the c.233 C>T p.Ser 78Leu of the MPZ gene (NM_000530.6) characterized as pathogenetic and the c.1403 G>A p.Arg 468His of the MFN2 gene (NM_014874.3) characterized as VUS. Concomitant variant mutations in CMTs have been uncommonly reported. The role of these gene mutations on the clinical expression and a literature review on this topic is discussed