Auto-Immunity Highlights最新文献

Current clinical experience with immunomodulatory agents and monoclonal antibodies in principle has established the benefit of depleting lymphocytic populations in relapsing-remitting multiple sclerosis (RRMS). B and T cells may exert multiple pro-inflammatory actions, but also possess regulatory functions making their role in RRMS pathogenesis much more complex. There is no clear correlation of Tregs and Bregs with clinical features of the disease. Herein, we discuss the emerging data on regulatory T and B cell subset distributions in MS and their roles in the pathophysiology of MS and its murine model, experimental autoimmune encephalomyelitis (EAE). In addition, we summarize the immunomodulatory properties of certain MS therapeutic agents through their effect on such regulatory cell subsets and their relevance to clinical outcomes.

Purpose: Indirect immunofluorescence (IIF) on the human epithelial cell-line HEp-2 (or derivatives) serves as the gold standard in antinuclear antibody (ANA) screening. IIF, and its evaluation, is a labor-intensive method, making ANA testing a major challenge for present clinical laboratories. Nowadays, several automated ANA pattern recognition systems are on the market. In the current study, the EUROPattern Suite is evaluated for its use in daily practice in a routine setting.

Methods: A total of 1033 consecutive routine samples was used to screen for ANA. Results (positive/negative ANA screening, pattern identification and titer) were compared between software-generated results (EUROPattern) and visual interpretation (observer) of automatically acquired digital images.

Results: Considering the visual interpretation as reference, a relative sensitivity of 99.3% and a relative specificity of 88.9% were obtained for negative and positive discrimination by the software (EPa). A good agreement between visual and software-based interpretation was observed with respect to pattern recognition (mean kappa: for 7 patterns: 0.7). Interestingly, EPa software distinguished more patterns per positive sample than the observer (on average 1.5 and 1.2, respectively). Finally, a concordance of 99.3% was observed within the range of 1 titer step difference between EPa and observer.

Conclusions: The ANA IIF results reported by the EPa software are in very good agreement with the results reported by the observer with respect to being negative/positive, pattern recognition and titer, making automated ANA IIF evaluation an objective and time-efficient tool for routine testing.

Introduction: This case uniquely reports a connection between endodontically infected teeth and systemic disease, and additionally presents ozone therapy as a unique therapy and immune system modulator. It is the world's first such reported case and the treatment holds invaluable lessons in assessing the "unknown" causes of autoimmunity and inflammation. Additionally, it presents ozone therapy as a most needed unique, non-toxic and powerful anti-infective agent, anti-inflammatory and immune modulator.

Case presentation: The patient was a Mexican male field laborer, age 48 years, in inflammatory crisis with a confirmed case of dermatomyositis. He had received massive prednisone, and powerful immune suppressing drugs just to function, while disease still raged. I encountered him in the field in June 2012 with severe muscle pain, weakness, and diffuse generalized skin rash, essentially unable to do his work. Creatine kinase peaked at 9293 U/L. History and physical examination findings caused suspicion of subclinical infections in endodontically treated teeth. This impression was confirmed in subsequent dental evaluation. He fully recovered after dental infections were confirmed and surgically removed, while receiving ozone therapy until all symptoms and laboratory abnormalities normalized.

Conclusion: Dental focus of occult infection may be a prime cause/trigger of autoimmune disorders and inflammatory disorders, requiring surgical intervention to remove. Ozone therapy, little known in conventional medicine, has been shown in the literature and in this case to be a powerful and safe immune modulator and anti-infective agent. This case has significant relevance across the entire spectrum of both medical and dental practice. It also emphasizes the need for individualized assessment and treatment rather than symptomatic pharmacological approaches treating a "disease" rather than the patient. Subclinical dental infection and ozone therapy are reviewed.

Purpose: Anti-phospholipid antibodies (aPL) analyzed by line immunoassay (LIA) can recognize beta₂-glycoprotein I (β₂GPI) domain 1 (D1) epitopes depending on β₂GPI binding to distinct phospholipids. The aPL LIA was compared with consensus ELISA to investigate whether both techniques can discriminate anti-phospholipid syndrome (APS) patients from aPL-positive, systemic autoimmune rheumatic diseases (SARD) patients without clinical symptoms of APS and controls.

Methods: Thirty-four APS patients (14 arterial/venous thrombosis, 16 pregnancy morbidity, and 4 both), 41 patients with SARD lacking clinical APS criteria but demonstrating positivity for anti-β₂GPI (aβ₂GPI) IgG, and 20 healthy subjects (HS) were tested for aPL to cardiolipin (aCL), phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol (aPG), phosphatidylinositol, phosphatidylserine, β₂GPI, prothrombin, and annexin V by LIA. Samples were also tested for aCL, aβ₂GPI, aβ₂GPI-domain 1 (aD1), and aβ₂GPI-domains 4-5 (aD4-5) by ELISA and for lupus anti-coagulant.

Results: Comparison of LIA with ELISA revealed a good agreement for the consensus criteria aPL aβ₂GPI and aCL IgG (kappa = 0.69, 0.68, respectively) and a moderate agreement for IgM (kappa = 0.52, 0.49, respectively). Regarding ELISA, aD1/aD4-5 demonstrated the best performance of differentiating APS from asymptomatic SARD [area under the curve (AUC): 0.76]. aPG IgG had the best performance by LIA (AUC: 0.72) not significantly different from aD1/aD4-5. There was a good agreement for aPG IgG with aD1/aD4-5 (kappa = 0.71).

Conclusions: aD1/aD4-5 (ELISA) and aPG IgG (LIA) differentiate APS from SARD patients. PG appears to interact with β₂GPI of APS patients and exposes D1 thereof for disease-specific aPL binding in LIA.

Systemic lupus erythematous (SLE) is a systemic auto-immune disorder with a variety of presentations and wide spread organ involvement. We present a case report of a patient with an SLE exacerbation as well as concurrent rhabdomyolysis with massively elevated CPK (304,700 U/L). Though a rarely reported effect of SLE, rhabdomyolysis can be severe and potentially lethal secondary or concurrent to an acute SLE episode. This case report demonstrates the association between SLE and rhabdomyolysis, which is not well described in the current literature.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease which has broad pleuropulmonary manifestations. One of the rare and mortal complications is acute lupus pneumonitis, which is reported very rarely, especially in childhood. Herein, we report an 8-year-old girl with isolated acute lupus pneumonitis as the initial presentation that required a lung biopsy for diagnosis. Although she had improvement with the administration of steroids, steroid treatment was reduced due to the drug's side effects resulting in the addition of azathioprine and mycophenolate mofetil to the treatment regimen. After the new regimen failed to result in clinical improvement, hydroxychloroquine treatment was started and a significant improvement was observed. Acute lupus pneumonitis is an uncommon manifestation of SLE and diagnosis may be difficult in patients without other organ involvement.

Purpose: Thyrotropin receptor (TSHR) autoantibodies (TRAbs) are a hallmark of Graves' disease (GD). The aim of this study was to evaluate the diagnostic accuracy of a new third generation automatic fluorescence enzyme immunoassay for TRAb measurement in GD, in comparison with two current IMAs.

Methods: Sera of 439 subjects (57 patients with untreated GD, 34 with treated GD, 15 with GD and Graves' orbitopathy, 52 with multinodular non-toxic goiter, 86 with Hashimoto's thyroiditis, 20 with toxic adenoma or toxic multinodular goiter, 55 with non-thyroid autoimmune diseases and 120 normal controls) were tested for TRAbs with the ELiA^™ anti-TSH-R assay (ThermoFischer Scientific, Uppsala, Sweden), the TRAK^™ RIA, Brahms (Thermo Scientific, Hennigsdorf, Germany) and the Immulite^™ TSI assay (Siemens Healthcare, Llanberis, UK).

Results: Sensitivity and specificity of the ELiA™ anti-TSH-R assay, TRAK™ RIA and Immulite™ TSI assay were 94.7% and 99.6, 100 and 98.2%, 100 and 98.2%, respectively. Spearman's coefficient and Passing-Bablok regression showed a satisfactory correlation between EliA™ and TRAK™ [rho: 0.925; 95% CI: 0.883-0-953. Intercept: - 0.875 (95% CI: - 2.411 to 0.194); slope: 1.086 (95% CI: 0.941 to 1.248)], and between ELiA^™ and TSI^™ [rho: 0.947; 95% CI: 0.912 0.969. intercept: 1.085 (95% CI: 0.665 to 2.116); slope 1.315 (95% CI:1.116 to 1.700)].

Conclusions: The diagnostic performance of ELiA^™-TSH-R assay is comparable to that of some current TRAb assays. It may be adopted into clinical practice for the differential diagnosis of hyperthyroidism, to screen for transient hyperthyroidism, and to monitor disease activity and treatment effects.

Vitamin D is one of the main groups of sterols; playing an important role in phospho-calcic metabolism. The conversion of 7-dehydrocholesterol to pre- vitamin D3 in the skin, through solar ultraviolet B radiation, is the main source of vitamin D. Since lupus patients are usually photosensitive, the risk of developing vitamin D deficiency in is high in this population. Although evidences showed the connotation between systemic lupus erythematosus (SLE) and vitamin D through which SLE can lead to lower vitamin D levels, it is also important to consider the possibility that vitamin D deficiency may have a causative role in SLE etiology. This paper analyzes existing data from various studies to highlight the role of vitamin D deficiency in SLE occurrence and aggravation and the probable efficacy of vitamin D supplementation on SLE patients. We searched "Science Direct" and "Pub Med" using "Vitamin D" and "SLE" for finding the studies focusing on the association between vitamin D deficiency and SLE incidence and consequences. Evidences show that vitamin D plays an important role in the pathogenesis and progression of SLE and vitamin D supplementation seems to ameliorate inflammatory and hemostatic markers; so, can improve clinical subsequent.

Purpose: The anion channel protein band 3 is the main target of the pathogenic red blood cells (RBC) autoantibodies in New Zealand black (NZB) mice. CD4 T cells from NZB mice with autoimmune hemolytic anemia respond to band 3. Previously, we have shown that IL-10 and peptides containing a dominant T cell epitope from red cell band 3 modulate autoimmune hemolytic anemia in NZB mice. Because of the immunoregulatory role of IL-10 in autoimmune diseases, we aim to identify individual band 3 peptides that induce high IL-10 production and simultaneously suppress CD4 T cell proliferation and to investigate the effect intranasal administration of IL-10 producing band 3 peptides on autoantibody responses of NZB mice.

Methods: Splenic CD4 T cells of NZB mice were isolated and stimulated by co-culture of T cells with individual band 3 peptides. IL-10 production was measured by enzyme-linked immunosorbent assay and proliferative response of CD4 T cells was estimated by incorporation of [³H] thymidine assay. NZB mice were given either PBS, or peptides 25 (241-251) and 29 (282-296) or both peptides intranasally on three occasions at 2-day intervals. The mice were bled at 6, 10 and 18 weeks after peptide inhalation, and the number of RBC auto-antibodies was measured by DELAT and hematocrit values were assessed.

Results: Peptides 25 (241-251) and 29 (282-296) induced the highest IL-10 production by CD4 T cells. These peptides also inhibited the peak T cell proliferative response. 6 and 10 weeks after peptide inhalation, the total IgG, IgG1 and IgG2a in mice treated with both peptides 241-251 and 282-296 were significantly higher than control (P < 0.05). However, no significant difference in the mean hematocrit between of the peptide-treated mice and the control group was found.

Conclusions: Although band 3 peptides 241-251 and 282-296 induced to the highest IL-10 production by CD4 T cells in vitro but fail to reverse the RBC autoantibody response in vivo. Modifications to improve solubility these peptides might help to modulate the immune response toward a T helper-2 profile and decrease the severity of anemia.