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Objectives: Belimumab is the first biologic drug approved for Systemic Lupus Erythematosus (SLE). Here, we aimed to investigate the effects of belimumab on clinical and serologic outcomes, and sought to identify predictors of treatment response in three Swedish real-life settings., Methods: Fifty-eight patients were enrolled at initiation of belimumab and followed longitudinally for up to 53months. Surveillance outcomes included the SLE Disease Activity Index 2000 (SLEDAI-2K), 100mm Visual Analogue Scales for Physician's Global Assessment (PGA), fatigue, pain and general health, and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Assessment of treatment response included the SLE responder index (SRI). B lymphocyte stimulator (BLyS) levels were determined using ELISA., Results: SLEDAI-2K (median baseline score: 8.0; IQR: 4.0-13.8), PGA and corticosteroid use decreased during therapy, and patients reported improvements on fatigue, pain, and general health (p<0.0001 for all). SDI scores remained stable (p=0.08). Patients with baseline SDI scores >1 showed decreased probability and prolonged time to attain SRI response (HR: 0.449; 95% CI: 0.208-0.967), as did current smokers compared with non-smokers (HR: 0.103; 95% CI: 0.025-0.427). In contrast, baseline BLyS levels ≥1.2ng/mL predicted increased probability and shorter time to attain SRI response (HR: 2.566; 95% CI: 1.222-5.387)., Conclusions: Disease activity and corticosteroid usage decreased, patient-reported outcomes improved, and no significant organ damage was accrued during follow-up. Smoking and organ damage predicted reduced treatment efficacy. These findings might contribute to a better selection of patients who are likely to benefit from belimumab., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: To investigate the prevalence and temporal development of N-methyl-d-aspartate receptor (NMDAR) autoantibodies in relation to neurocognitive performance in patients with herpes simplex encephalitis (HSE)., Methods: This prospective observational study enrolled a total of 49 HSE patients within a randomized controlled trial of valacyclovir. Cerebrospinal fluid and serum samples were drawn in the initial stage of disease, after 2 to 3 weeks and after 3 months. Anti-NMDAR IgG was detected with HEK293 cells transfected with plasmids encoding the NMDA NR1 type glutamate receptor. A batch of neurocognitive tests, including the Mattis Dementia Rating Scale (MDRS), Glasgow Coma Scale (GCS), Reaction Level Scale (RLS85), Mini-Mental State Examination (MMSE) and National Institutes of Health (NIH) stroke scale, was performed during 24 months' follow-up., Results: Anti-NMDAR IgG was detected in 12 of 49 participants. None were antibody positive in the initial stage of disease. In ten of 12 positive cases, specific antibodies were detectable only after 3 months. Notably, the development of NMDAR autoantibodies was associated with significantly impaired recovery of neurocognitive performance. After 24 months' follow-up, the median increase in MDRS total score was 1.5 vs. 10 points in antibody-positive and -negative participants (p=0.018)., Conclusions: Anti-NMDAR autoimmunity is a common complication to HSE that develops within 3 months after onset of disease. The association to impaired neurocognitive recovery could have therapeutical implications, as central nervous system autoimmunity is potentially responsive to immunotherapy., (Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Leishmaniasis is a neglected disease in tropical countries. Clinical and laboratory features may mimic autoimmune diseases and this can complicate the Leishmania diagnosis. Due to our previous investigation for false anti-CCP2 reactivity in Leishmania-infected subjects and our interest in immunity against the joint-specific collagen type II (CII) in rheumatoid arthritis (RA) we investigated the same cohort for anti-CII antibodies. We found elevated anti-CII reactivity in Leishmania-infected patients as compared to controls. When anti-CII OD values were compared with BSA-blocked control plates we found higher reactivity against BSA than in CII-coated plates in many Leishmania-infected patients. The percentage of such false positive anti-CII reactions increased with inflammatory activity, and was found in almost all Leishmania patients with highly active inflammatory disease, but was as low in Sudanese healthy controls as well as among Swedish RA patients. The correlation coefficients between false positive anti-CII and anti-CCP2 measured with a commercial ELISA were highest for patients with the most inflammatory disease but non-significant for Sudanese controls and Swedish RA patients, arguing that our findings may have general implications for ELISA measurements in leishmaniasis. ELISA investigations in areas endemic for leishmaniasis might benefit from individual-specific control wells for each serum sample. This approach might also be applicable to other geographical areas or patient groups with high incidence of inflammatory and infectious diseases., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: The pathophysiology of the postpolio syndrome is not fully understood. Increased cytokine levels in cerebrospinal fluid and peripheral blood indicate a systemic inflammatory process. Decreased cytokine levels and the clinical effect of intravenous immunoglobulin treatment further indicate an inflammatory/immunological pathogenesis. The aim of the present study was to evaluate whether an autoimmune process follows the initial infection, by means of analyzing immune complexes., Patients and Methods: Circulating immune complexes were analyzed from blood samples of 20 postpolio patients and 95 healthy controls. To compensate for differences in age between patients and controls, a sub-analysis was performed using only the 30 oldest controls. Tumor necrosis factor-inducing properties of polyethylene glycol-precipitated immune complexes were compared between the postpolio patients and 10 healthy controls., Results: When comparing levels in postpolio patients to the whole control group, including the 30 oldest investigated, there were no statistically significant differences. No difference was found in tumor necrosis factor levels induced by immune complexes when comparing patients and controls., Conclusions: There was no increase in circulating immune complex or in tumor necrosis factor-inducing effects of circulating immune complex between postpolio patients and healthy controls, indicating that the postpolio syndrome is not due to an autoimmune reaction.

Aims: To evaluate the clinical utility of a commercial immunoblot assay for the detection of myositis-specific autoantibodies., Methods: Serum samples from 153 myositis patients and 77 disease controls were investigated. The commercial Euroline assay with seven autoantigens (Mi-2, Ku, PM-Scl, Jo-1, Pl-7, Pl-12 and SSA/Ro-52) was used according to the manufacturer s instructions, and supplemented with an anti-SRP strip. In a separate experiment analyses were performed at different temperatures. Results were recorded with densitometry., Results: Anti-Jo-1 was found in 18 myositis and one systemic sclerosis patient. Antibodies against Mi-2 were found in 5 myositis patients, and eleven myositis patients had antibodies against PM-Scl. Four myositis patients showed anti-Pl-7 reactivity, whereas no patients had antibodies against Pl-12. Anti-Ku antibodies were found in 4 myositis and 2 primary Sjögren's syndrome patients. Anti-SRP was found in 8 myositis patients as well as in two disease controls. Antibodies against SSA/Ro52 ranged between 23-62% in all groups except juvenile dermatomyositis patients. Most autoantibody reactivities were clearly positive, only 11% (14/127) were borderline positive. Higher assay temperature increased antibody reactivities., Conclusions: Except for anti-SSA/Ro-52 and anti-Ku the antibody reactivities were rather myositis-specific, supporting the use of this immunoblot assay. However, assay validation needs to be determined against other methods.

The combined role of genes, environment and immunity in the development of rheumatoid arthritis (RA) has been the subject of recent investigations. New data support a gene-environment interaction between smoking and the MHC class II HLA-DRB1 shared epitope (SE) genes in anti-citrulline antibody (anti-CP(+)) RA but not in anti-CP(-) disease. These data from genetic epidemiology, together with information on citrullination in the lungs of smokers, have prompted the formulation of a new etiological hypothesis for anti-CP(+) RA, suggesting that smoking in the context of HLA-DR SE might trigger immunity to citrulline-modified proteins and that this immunity, after several years, might cause arthritis.

We have used the ELISPOT method employing plastic ELISA plates without substrate in agar for the detection of single cells producing interferon-gamma (IFN-gamma) and interleukin-4 (IL-4). When using PBMC directly stimulated in the assay wells with T cell mitogens it was possible to measure production of human IFN-gamma at an earlier time point and with a higher sensitivity compared to conventional nitrocellulose plates. The plastic surface was not autostimulatory for IFN-gamma production, as seems to be the case for nitrocellulose surfaces. Compared to the use of nitrocellulose plates, the use of plastic ELISA plates is considerably cheaper and easier to perform. The increased sensitivity for cytokine detection, together with minimal autostimulatory properties of the detection surface, makes this method suitable for the detection of spontaneous low grade cytokine production from cells obtained in vivo.

The immunopathogenesis of rheumatoid arthritis is discussed in two ways. First, we consider the major question of whether T cells are likely to drive the disease. Second--and assuming T cells to be important--we discuss available data on the components of the trimolecular complex (major histocompatibility complex class II-antigen-T-cell receptor), which are possibly involved in the disease. Our two main points are that the most important questions concerning the pathogenesis of rheumatoid arthritis require answers from immunointervention in patients, and that animal experiments can be increasingly used in interpreting current experiments in humans.