Non-infectious meningitis and CNS demyelinating diseases: A conceptual review.

Many cases of aseptic meningitis or meningoencephalitis, unresponsive to antimicrobial treatments, have been reported recently in patients with established/new-onset central nervous system (CNS) inflammatory demyelinating diseases (CNSIDDs). Given the higher probability of infectious etiologies, CNSIDDs are rarely considered among the differentials in meningitis or meningoencephalitis cases. We gathered and tabulated cases of non-infectious, steroid-responsive meningitis or meningoencephalitis associated with neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-associated disease (MOGAD). This conceptual review highlights the need to bolster routine infectious workups with immunological workups in cases of meningoencephalitis or meningitis where potential autoimmune etiologies can be suspected. Although differentiating CNSIDDs with meningeal involvement from infectious meningitis may not substantially affect acute treatment strategies, long-term management and follow-up of the two are entirely different. We also discuss future research directions and hypotheses on how CNSIDDs may be associated with meningitis-like presentations, e.g. overlapping glial fibrillary acidic protein astrocytopathy or autoimmune encephalitis, alterations in regulatory T-helper cells function, and undetected viral agents.

Increased IRF4 expression in isolated B cells from common variable immunodeficiency (CVID) patients

Background: Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by low serum levels of immunoglobulins (Igs) and recurrent infection. In most CVID patients, a defect in the differentiation of B cells into plasma cells has been observed. Several factors play an important role in the proliferation and differentiation of B cells, including IRF4 and XBP1 transcription factors. Methods: In the present study we investigated the expression of IRF4 and XBP1 in the B-cells of CVID and healthy controls (HCs). For this purpose, we assessed the expression of IRF4 and XBP1 at both mRNA and protein levels by real time-PCR and flow cytometry, respectively. Results: We found that IRF4 expression was significantly increased in CVID patients compared with controls. Although the XBP1 protein level was lower in patients in comparison to controls, this difference was not significant. Conclusion: Taken together, increased IRF4 expression could be involved in defective functions of B cells in CVID patients

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Features and roles of T helper 9 cells and interleukin 9 in immunological diseases

T helper 9 (TH9) cells are considered as newly classified helper T cells that have an important role in the regulation of immune responses. Since these cells preferentially produce IL-9, these cells are termed TH9 cells. Recently, the role of TH9 and its signature cytokine (IL-9) has been investigated in a wide range of diseases, including autoimmunity, allergy, infections, cancer and immunodeficiency. Herein, we review the most recent data concerning TH9 cells and IL-9 as well as their roles in disease. These insights suggest that TH9 cells are a future target for therapeutic intervention

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Features and roles of T helper 9 cells and interleukin 9 in immunological diseases.

T helper 9 (TH9) cells are considered as newly classified helper T cells that have an important role in the regulation of immune responses. Since these cells preferentially produce IL-9, these cells are termed TH9 cells. Recently, the role of TH9 and its signature cytokine (IL-9) has been investigated in a wide range of diseases, including autoimmunity, allergy, infections, cancer and immunodeficiency. Herein, we review the most recent data concerning TH9 cells and IL-9 as well as their roles in disease. These insights suggest that TH9 cells are a future target for therapeutic intervention.

Correlation of OX40 ligand on B cells with serum total IgE and IL-4 levels by CD4+ T cells in allergic rhinitis.

INTRODUCTION AND OBJECTIVES: Allergic rhinitis (AR) is a classic Th2-mediated disease, with important contributions to the pathology of interleukins 4, 5, and 13. The co-stimulatory molecule of OX40 and its ligand interaction participate in the immune response by regulation of Th1/Th2 cells balance. Considering the paucity of information on the relation between OX40 ligand (OX40L) and AR, this study aimed to examine its expression on B lymphocytes. PATIENTS AND METHODS: This case-control study consisted of 20 AR patients and 20 healthy subjects. The serum level of total immunoglobulin E (IgE) was measured using the electro-chemiluminescence (ECL) technology. The percentage of B-lymphocytes expressing OX40L was assessed by flow cytometry. The amounts of IL-4 in CD4+ T cells culture supernatant was also measured by the enzyme-linked immunosorbent assay (ELISA). RESULTS: OX40L expression on B lymphocytes of patients was significantly higher than the control group (44.32±19.21% vs. 2.79±2.48% respectively, p<0.001). In AR patients, OX40L expression correlated positively with the levels of serum total IgE and IL-4 produced by CD4+ T lymphocytes (p<0.01 - p<0.05) respectively. CONCLUSIONS: Collectively, the findings of this work suggest that there is a relationship between the OX40L expression level on B lymphocytes and allergic markers such as IgE and IL-4 in patients with allergic rhinitis.

Increased IRF4 expression in isolated B cells from common variable immunodeficiency (CVID) patients.

BACKGROUND: Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by low serum levels of immunoglobulins (Igs) and recurrent infection. In most CVID patients, a defect in the differentiation of B cells into plasma cells has been observed. Several factors play an important role in the proliferation and differentiation of B cells, including IRF4 and XBP1 transcription factors. METHODS: In the present study we investigated the expression of IRF4 and XBP1 in the B-cells of CVID and healthy controls (HCs). For this purpose, we assessed the expression of IRF4 and XBP1 at both mRNA and protein levels by real time-PCR and flow cytometry, respectively. RESULTS: We found that IRF4 expression was significantly increased in CVID patients compared with controls. Although the XBP1 protein level was lower in patients in comparison to controls, this difference was not significant. CONCLUSION: Taken together, increased IRF4 expression could be involved in defective functions of B cells in CVID patients.

Comparison of various classifications for patients with common variable immunodeficiency (CVID) using measurement of B-cell subsets

BACKGROUND: Common variable immunodeficiency (CVID) is a heterogeneous disease, characterised by hypogammaglobulinaemia leading to recurrent infections and various complications. The aim of this study was to classify CVID patients based on four known classifications (Paris, Freiburg, EUROclass, and B-cell patterns) by measurement of B-cell subsets and to assess the relation of each classification with clinical manifestations. METHODS: We measured all B-cell subsets as both absolute count and percentage in 30 CVID patients and 30 healthy individuals using four-colour flow cytometry. Moreover, we evaluated antibody responses to pneumococcal vaccine in patients. RESULTS: A significant reduction in percentage of terminal B-cell subsets (total, marginal zone-like, switched memory, IgM-only memory, total memory B-cells and plasmablast) and absolute count of all B-cell subsets along with a strong increase in CD21low B-cells has been observed in patients. Patients with splenomegaly and hepatomegaly clustered in group Ia, smB+21low and group 1 based on known classifications, and significantly tended to have a decreased transitional and marginal zone-like B-cells count, as well as an increase in CD21low B-cell counts. Patients with lymphadenopathy, bronchiectasis and allergy had a significant decrease in absolute count of total memory, switched memory and total B-cells, respectively. CONCLUSION: Classification of patients could provide useful information to guide clinicians in long-term follow-up of CVID patients. Our data demonstrate that it may be more accurate to use absolute counts of B-cell subpopulations in CVID patients because absolute counts of B-cell subsets are more associated with clinical manifestations compared with their percentage and also four known classifications

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Comparison of various classifications for patients with common variable immunodeficiency (CVID) using measurement of B-cell subsets.

BACKGROUND: Common variable immunodeficiency (CVID) is a heterogeneous disease, characterised by hypogammaglobulinaemia leading to recurrent infections and various complications. The aim of this study was to classify CVID patients based on four known classifications (Paris, Freiburg, EUROclass, and B-cell patterns) by measurement of B-cell subsets and to assess the relation of each classification with clinical manifestations. METHODS: We measured all B-cell subsets as both absolute count and percentage in 30 CVID patients and 30 healthy individuals using four-colour flow cytometry. Moreover, we evaluated antibody responses to pneumococcal vaccine in patients. RESULTS: A significant reduction in percentage of terminal B-cell subsets (total, marginal zone-like, switched memory, IgM-only memory, total memory B-cells and plasmablast) and absolute count of all B-cell subsets along with a strong increase in CD21low B-cells has been observed in patients. Patients with splenomegaly and hepatomegaly clustered in group Ia, smB+21low and group 1 based on known classifications, and significantly tended to have a decreased transitional and marginal zone-like B-cells count, as well as an increase in CD21low B-cell counts. Patients with lymphadenopathy, bronchiectasis and allergy had a significant decrease in absolute count of total memory, switched memory and total B-cells, respectively. CONCLUSION: Classification of patients could provide useful information to guide clinicians in long-term follow-up of CVID patients. Our data demonstrate that it may be more accurate to use absolute counts of B-cell subpopulations in CVID patients because absolute counts of B-cell subsets are more associated with clinical manifestations compared with their percentage and also four known classifications.

Association of TIM-1 5383-5397ins/del and TIM-3 -1541C>T polymorphisms with multiple sclerosis in Isfahan population.

Multiple sclerosis (MS) is an organ-specific autoimmune disease in central nervous system, affecting about 2.5 million people around the world. Probable involvement of two newly identified immunoregulator molecules, TIM-1 and TIM-3, has been reported in autoimmune diseases. In this study, for the first time, the association of TIM-1 5383-5397ins/del and TIM-3 -1541C>T polymorphisms with MS in an Iranian population was considered. The results of our study showed that there is no significant association between TIM-1 5383-5397ins/del and MS (P = 0.38); however, the frequency of CT genotype of TIM-3 -1541C>T in patient group was significantly higher than the control group, and there was a significant association between CT genotype and MS (P = 0.009, OR = 4.08).

Association analysis of -416 G>C polymorphism of T-cell immunoglobulin and mucin domain-1 gene with asthma in Iran.

TIM (T-cell immunoglobulin (Ig) and mucin domain)-1, one of the members of TIM family, expresses on Th2 cells and promotes the production of Th2 signature cytokines. This can increase a series of responses in these cells which could be one of the causes of asthma or asthma-related phenotypes. The aim of this study was to investigate whether a TIM-1 promoter single nucleotide polymorphism (SNP), -416 G>C, is associated with asthma in Iranian population. In this case-control study, existence of the -416 G>C polymorphism was assessed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) in 300 patients with asthma (97 atopic, 203 nonatopic) and 309 healthy volunteers. Additionally, the relationship between these polymorphism genotypes and total serum IgE levels in this Iranian population was evaluated. We discovered a significant association between the -416 G>C polymorphism and atopic asthma susceptibility in the population, but this SNP showed no connection with nonatopic asthma (P < 0.05). However, our results showed significant relation between this polymorphism and serum IgE level (P < 0.05). Our results suggest that -416 G>C polymorphism in TIM-1 gene could be a predisposing factor for atopic asthma in Iranian population, and CC genotype of this SNP can be associated with increased level of IgE in patients with asthma in the same population.

Signs of the presence of Th17 cells in chronic periodontal disease.

BACKGROUND AND OBJECTIVE: The aim of this study was to identify the specific markers of T helper 17 (Th17) cells and their variations in people suffering from chronic periodontal disease in comparison with normal control subjects. MATERIAL AND METHODS: In 30 patients with periodontitis and 30 normal control subjects, the mRNA expressions of interleukin (IL)-17A and retinoic orphan receptor C2 (RORC2) were measured by quantitative RT-PCR. The protein levels of IL-17A and RORC2 were also evaluated by immunohistochemistry. The levels of these markers were compared between healthy and diseased periodontal tissues by the Mann-Whitney U-test. RESULTS: In periodontal lesions, IL-17A and RORC2 were significantly overexpressed compared with normal tissues. According to our immunohistochemical analysis, the number of IL-17A-positive cells and RORC2-positive cells was significantly greater in periodontal lesions compared with control sites. Moreover, there was a positive correlation between the presence of IL-17A and RORC2 transcript and protein content levels in the gingiva of diseased patients. CONCLUSION: The results demonstrated a significant increase in the number of some specific markers of Th17 cells in patients suffering from periodontal disease in comparison with normal control subjects.

Chronic kidney disease after hematopoietic cell transplantation: frequency, risk factors, and outcomes.

BACKGROUND: Occurrence of chronic kidney disease (CKD) after hematopoietic cell transplantation (HCT) is rare with relatively few reported cases. The aim of this study was to evaluate the frequency of CKD among patients who received HCT for hematologic and nonhematologic disorders. OBJECTIVE: We performed a prospective study to evaluate the frequency of CKD and its risk factors. Between 1997 and 2006 there were 1693 patients engrafted at the Bone Marrow Transplant Research Center. METHOD: CKD was defined as a doubling of serum creatinine level from the baseline and after 1 year from receiving a transplantation. The risk of CKD in relation to a non-based total body irradiation conditioning regimen, the type of graft (allograft autograft), and the incidences of graft-versus-host disease (GVHD), drug toxicity, and veno occlusive disease (VOD) were examined in 1963 HCT patients. RESULTS: Kidney involvement developed in 66 patients (4%). By 6-12 months after HCT, approximately 33% of these patients developed CKD (23 patients: 19 allograft and 4 autograft). In most CKD patients, the cause was idiopathic. In 23 patients who developed CKD, 5 patients had acute kidney injury during the transplantation period with GVHD. Other renal involvements were as follows: hypertension (17%), proteinuria (15%), hydronephrosis (2%), hematuria (18%), and diabetes (3%). CONCLUSION: The frequency of CKD in this study seems to be high. It is important to know the specific type of kidney damage, to determine when to be aware of the time of occurrence of renal complications and to understand the best methods to treat patients with renal injury secondary to nephrotic syndrome and idiopathic CKD.

Socioeconomic status of Iranian living unrelated kidney donors: a multicenter study.

Renal transplantation is the best treatment modality for end-stage renal disease (ESRD) patients. In Iran, a living unrelated donor (LURD) transplant program was started in 1988, because of the shortage of living related and cadaver donors. In this study, we evaluated the socioeconomic status of LURD in Iran. We enrolled 478 LURDs from 30 transplant centers between October 2005 and March 2006. The demographic data, education, employment, motivation, and satisfaction status were asked. Economic status was assessed using criteria of the statistics center of Iran. Ninety-six percent of donors were referred from the Kidney Foundation of Iran (KFI). The mean age of the donors was 27 +/- 4.8 years and 85% were men (n=408). Fifty-one percent were smokers, 82% married, and 79% the breadwinner; 29% were unemployed; 2.7%, 90.8%, and 6.5% were illiterate, school graduates, and university graduates, respectively. Coercion was documented for only one donor. Financial issues were the most frequent motive. Among them, 91% were satisfied with the donation. Finally, 53% suggested kidney donation to others. Of donors, 62% were living below the poverty line. In the Iran model, the KFI is a bridge that connects recipients and donors. As a result, there is no middle man or broker introducing donors to recipients. The transplantation team knows nothing about money transactions between recipient and donor. Most donors were satisfied with the donation. However, establishment of a government-regulated program for social support of donors, such as lifelong health insurance may be a compensation for donors.

Association of hyperglycemia on allograft function in the early period after renal transplantation.

Hyperglycemia is common following renal transplantation. This study was conducted to evaluate the relationship of perioperative serum glucose levels and acute rejection in 100 nondiabetic patients who underwent renal transplantation. Blood glucose was measured immediately following surgery and every 6 hours during the first 48 hours posttransplant as well as for 1 month to evaluate occurrence of acute rejection episodes (ARE). The rate of ARE was 33%. The mean blood glucose level immediately after surgery in patients with versus without ARE was 249.67 +/- 61.78 and 184.82 +/- 73.35 mg/dL, respectively (P=.000). There was no significant correlation between ARE and donor or recipient age or sex, delayed graft function, type of donor, or treatment. This study suggested a correlation between immediate blood glucose and ARE. In this regard, blood glucose monitoring and control during operation and immediate postoperatively may reduce the acute rejection rate.