Immunological Features Of Patients Research Articles

Late-onset versus early-onset systemic lupus: characteristics and outcome in a national multicentre register (RELESSER).

The aim of the present study was to describe the demographic, clinical and immunological characteristics of patients with late-onset (≥50 years) SLE vs patients with early-onset SLE (<50 years). We performed a cross-sectional retrospective study of 3619 patients from the RELESSER database (National Register of Patients with Systemic Lupus Erythematosus of the Spanish Society of Rheumatology). A total of 565 patients (15.6%) were classified as late-onset SLE and 3054 (84.4%) as early-onset SLE. The male-to-female ratio was 5:1. Mean (s.d.) age at diagnosis in the late-onset group was 57.4 (10.4) years. At diagnosis, patients with late-onset SLE had more comorbid conditions than patients with early-onset SLE; the most frequent was cardiovascular disease (P<0.005). Furthermore, diagnostic delay was longer in patients with late-onset SLE [45.3 (3.1) vs 28.1 (1.0); P<0.001]. Almost all patients with late-onset SLE (98.7%) were Caucasian. Compared with early-onset SLE and after adjustment for time since diagnosis, patients with late-onset SLE more frequently had serositis, major depression, thrombotic events, cardiac involvement and positive lupus anticoagulant values. They were also less frequently prescribed immunosuppressive agents. Mortality was greater in late-onset SLE (14.3% vs 4.7%; P<0.001). Late-onset SLE is insidious, with unusual clinical manifestations that can lead to diagnostic errors. Clinical course is generally indolent. Compared with early-onset disease, activity is generally reduced and immunosuppressants are less commonly used. Long-term prospective studies are necessary to determine whether the causes of death are associated with clinical course or with age-associated comorbidities in this population.

Transcriptional and proteomic insights into the host response in fatal COVID-19 cases

Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, has resulted thus far in greater than 933,000 deaths worldwide; yet disease pathogenesis remains unclear. Clinical and immunological features of patients with COVID-19 have highlighted a potential role for changes in immune activity in regulating disease severity. However, little is known about the responses in human lung tissue, the primary site of infection. Here we show that pathways related to neutrophil activation and pulmonary fibrosis are among the major up-regulated transcriptional signatures in lung tissue obtained from patients who died of COVID-19 in Wuhan, China. Strikingly, the viral burden was low in all samples, which suggests that the patient deaths may be related to the host response rather than an active fulminant infection. Examination of the colonic transcriptome of these patients suggested that SARS-CoV-2 impacted host responses even at a site with no obvious pathogenesis. Further proteomics analysis validated our transcriptome findings and identified several key proteins, such as the SARS-CoV-2 entry-associated protease cathepsins B and L and the inflammatory response modulator S100A8/A9, that are highly expressed in fatal cases, revealing potential drug targets for COVID-19.

More Severe Erosive Phenotype Despite Lower Circulating Autoantibody Levels in Dipeptidyl Peptidase-4 Inhibitor (DPP4i)-Associated Bullous Pemphigoid: A Retrospective Cohort Study.

BackgroundThe clinical and immunological profile of patients with dipeptidyl peptidase-4 inhibitor (DPP4i)-associated bullous pemphigoid (BP) is inconsistent in the current literature.ObjectivesThe aims were to investigate the clinical and immunological features of patients with DPP4i-associated BP and to examine whether there are intraclass differences between different DPP4i agents.MethodsA retrospective cohort study was conducted, including all consecutive patients diagnosed with BP throughout the years 2009–2019 in a tertiary referral center.ResultsThe study encompassed 273 patients with BP (mean age at diagnosis 79.1 ± 9.9 years), of whom 24 (8.8%) were associated with DPP4i. Sitagliptin was the prescribed agent for 17 patients (70.8%), and vildagliptin was prescribed in seven patients (29.2%). Relative to other patients with BP, patients with DPP4i-associated BP had more prominent truncal involvement (95.8% vs. 73.9%; P = 0.017), greater erosion/blister Bullous Pemphigoid Disease Area Index (BPDAI) subscore (29.8 ± 17.4 vs. 20.6 ± 14.4; P = 0.018), and lower levels of anti-BP180 NC16A (279.2 ± 346.1 vs. 572.2 ± 1352.0 U/ml; P = 0.009) and anti-BP230 (25.5 ± 47.8 vs. 128.6 ± 302.9 U/ml; P = 0.009) antibodies. Relative to patients with sitagliptin-associated BP, those with vildagliptin-associated BP had a lower seropositivity rate (57.1% vs. 94.1%, P = 0.031) and lower levels (96.7 ± 139.0 vs. 354.5 ± 376.5; P = 0.023) of anti-BP180 NC16A antibodies, and tended to present with higher erosion/blister BPDAI subscore (36.3 ± 9.6 vs. 25.8 ± 19.7; P = 0.095).ConclusionsDPP4i-associated BP is characterized by a more severe blistering and erosive presentation despite lower levels of typically pathogenic antibodies.

Immunological features of patients affected by Barraquer-Simons syndrome

BackgroundC3 hypocomplementemia and the presence of C3 nephritic factor (C3NeF), an autoantibody causing complement system over-activation, are common features among most patients affected by Barraquer-Simons syndrome (BSS), an acquired form of partial lipodystrophy. Moreover, BSS is frequently associated with autoimmune diseases. However, the relationship between complement system dysregulation and BSS remains to be fully elucidated. The aim of this study was to provide a comprehensive immunological analysis of the complement system status, autoantibody signatures and HLA profile in BSS. Thirteen subjects with BSS were recruited for the study. The circulating levels of complement components, C3, C4, Factor B (FB) and Properdin (P), as well as an extended autoantibody profile including autoantibodies targeting complement components and regulators were assessed in serum. Additionally, HLA genotyping was carried out using DNA extracted from peripheral blood mononuclear cells.ResultsC3, C4 and FB levels were significantly reduced in patients with BSS as compared with healthy subjects. C3NeF was the most frequently found autoantibody (69.2% of cases), followed by anti-C3 (38.5%), and anti-P and anti-FB (30.8% each). Clinical data showed high prevalence of autoimmune diseases (38.5%), the majority of patients (61.5%) being positive for at least one of the autoantibodies tested. The HLA allele DRB1*11 was present in 54% of BSS patients, and the majority of them (31%) were positive for *11:03 (vs 1.3% allelic frequency in the general population).ConclusionsOur results confirmed the association between BSS, autoimmunity and C3 hypocomplementemia. Moreover, the finding of autoantibodies targeting complement system proteins points to complement dysregulation as a central pathological event in the development of BSS.

Characteristics of patients with systemic sclerosis living in Qatar.

Objective: The aim of this study was to determine the demographic, clinical, and immunological characteristics of patients with systemic sclerosis living in Qatar. Method: This retrospective study included 42 patients with systemic sclerosis who attended Rheumatology Clinics at Hamad General Hospital in Doha, Qatar, between January 2000 and December 2014. All patients fulfilled the 1980 American College of Rheumatology (ACR) classification criteria for systemic sclerosis. Results: The 42 consecutively recruited patients of mixed ethnicities consisted of 37 (88.1%) females and 5 (11.9%) males. Of the total 42 patients, 22 (52.4%) had diffuse cutaneous systemic sclerosis (dcSSc) and 20 (47.6%) had limited cutaneous systemic sclerosis (lcSSc). Mean age at onset of first symptoms was 34.5 ± 12 years, and mean age at diagnosis was 36.1 ± 11.5 years. During follow-up, Raynaud's phenomenon occurred in 36 (85.7%) patients, sclerodactyly in 39 (92.9%) patients, digital ulcers in 16 (38.1%) patients, calcinosis in 6 (14.3%) patients, telangiectasia in 16 (38.1%) patients, and arthritis in 13 (31%) patients. The gastrointestinal and respiratory systems were the most frequently affected internal organs. Gastrointestinal involvement was present in 36 (85.7%) patients, and respiratory involvement was found in 30 (71.4%) patients. The majority of patients had positive antinuclear antibodies (ANA; 97.6%). Anti-Scl-70 antibody was found in 66.7% and anti-centromere antibody (ACA) was detected in 14.3% of the patients. Conclusion: To our knowledge, this is the first study that describes the clinical and immunological profile of patients with systemic sclerosis living in Qatar. This study cohort showed an earlier age of disease onset and diagnosis than that reported in other international studies. Furthermore, in contrast to several other studies, the diffuse type of scleroderma was more commonly observed than the limited type, which resulted in a high frequency of anti-Scl-70 antibody and interstitial lung disease.

The immunologic features of patients with early-onset and polyautoimmunity

Inflammatory conditions are increasingly described in patients with primary immunodeficiencies; however, little is known about the prevalence of immune defects in patients who present first with autoimmunity. We describe the immunologic features of children with early-onset/polyautoimmunity followed in the Multiple Autoimmunity and Immunodeficiency (MAID) Clinic, where patients are co-managed by rheumatologists and immunologists. The most common autoimmune manifestations were cytopenias, lymphoproliferation, and colitis. Recurrent infections were noted in 65% of patients. Abnormalities in lymphocyte subsets and immunoglobulins were common. A pathogenic variant was identified in 19% of patients, and 2 novel inherited disorders were discovered. Additionally, 42% of patients had treatment changes implemented in the MAID clinic. By evaluating this unique cohort of patients, we report on the immunologic underpinning of early-onset/polyautoimmunity. The high rate of genetic diagnoses and treatment interventions in this population highlights the value of collaboration between rheumatologists and immunologists in the care of these complex patients.

Clinical characteristics and survival of 413 patients with systemic lupus erythematosus in southeastern areas of South Korea: A multicenter retrospective cohort study.

To investigate demographic, clinical, laboratory, and immunological characteristics of patients with systemic lupus erythematosus (SLE) in southeastern areas of South Korea, and to perform survival analysis. We retrospectively evaluated 413 patients with SLE diagnosed in 3 tertiary rheumatology centers in South Korea from 1992 to 2016 by reviewing their medical charts. All patients fulfilled the 1997 revised American College of Rheumatology classification criteria for SLE. Most patients were women (92%), and the mean (±standard deviation) age at diagnosis was 30.9 (±12.9) years. The most common clinical manifestation was leukopenia (74.3%), followed by lymphopenia (73.6%), arthritis (59.1%), malar rash (48.4%), thrombocytopenia (46.5%), oral ulcer (35.1%), and biopsy-proven lupus nephritis (31.2%). Anti-nuclear, anti-double-stranded DNA, anti-Smith, and anti-Ro antibodies were positive in 97.8%, 70.1%, 38.4%, and 63% of patients, respectively. Twenty (4.8%) patients died during a median follow-up of 83months, and the cumulative 5-year and 10-year survival rates were 96.9% and 95.5%, respectively. The major causes of death were infection (50%) and lupus flare-up (50%). Male (hazards ratio [HR]=7.19, P=.001), pleuritis and/or pericarditis (HR=3.28, P=.012), childhood-onset (HR=3.57, P=.012), and late-onset (HR=4.65, P=.011) were independent risk factors for death. Compared with SLE cohorts in other ethnicities or countries, our patients tended to have a higher frequency of anti-Ro antibodies and hematologic disorders. This study describes clinical features of SLE in South Korea and suggests a remarkable phenotypic heterogeneity of SLE.

The Relationship Between Tumor-Stroma Ratio, the Immune Microenvironment, and Survival in Patients With Spinal Chordoma.

Currently, little is known about the clinical relevance of tumor-stroma ratio (TSR) in chordoma and data discussing the relationship between TSR and immune status of chordoma are lacking. To characterize TSR distribution in spinal chordoma, and investigated its correlation with clinicopathologic or immunological features of patients and outcome. TSR was assessed visually on hematoxylin and eosin-stained sections from 54 tumor specimens by 2 independent pathologists. Multiplex immunofluorescence was used to quantify the expression levels of microvessel density, Ki-67, Brachyury, and tumor as well as stromal PD-L1. Tumor immunity status including the Immunoscore and densities of tumor-infiltrating lymphocytes (TILs) subtypes were obtained from our published data and reanalyzed. Bland-Altman plot showed no difference between mean TSR derived from the two observers. TSR was positively associated with stromal PD-L1 expression, the Immunoscore and CD3+ as well as CD4+ TILs density, but negatively correlated with tumor microvessel density, Ki-67 index, surrounding muscle invasion by tumor and number of Foxp3+ and PD-1+ TILs. Low TSR independently predicted poor local recurrence-free survival and overall survival. Moreover, patients with low TSR and low Immunoscore chordoma phenotype were associated with the worst survival. More importantly, combined TSR and Immunoscore accurately reflected prognosis and enhanced the ability of TSR or Immunoscore alone for outcome prediction. These data reveal the significant impact of TSR on tumor progression and immunological response of patients. Subsequent use of agents targeting the stroma compartment may be an effective strategy to treat chordoma especially in combination with immune-based drugs.

Features of the course of polypous rhinosinusitis combined with allergic rhinitis

Both allergic rhinitis (AR) and polypous rhinosinusitis (PRS) are a serious problem in context of their impact on quality of life, the risk of complications, overlay of bronchial asthma (BA) and medical control of these diseases. In most cases, T2 type eosinophilic inflammation lies beneath their pathogenesis, but the mutual influence of simultaneously existing chronic processes on each other appears under-investigated. Objective of the study: Compare the clinical and immunological characteristics of patients with polypous rhinosinusitis and concomitant allergic rhinitis and without respiratory allergy. All patients with PRS were divided into 2 phenotypic groups: Group 1 – PRS without bronchial asthma and respiratory allergy (54 people), Group 2 - PRS + allergic rhinitis, but without bronchial asthma (46 people). IL-1β-, IL-4-, IL-5-, IL-6-, IL-13-, IFN-γ-, TGF-β1-, TGF-β2-, TGF β-3 cytokines in nasal polyp tissue were determined using the Bio-Plex multiplex analysis system. Results: In patients with PRS combined with AR, the eosinophilic type of inflammation in the polyp tissue was determined in 100% of cases, it was accompanied by an increased level of IL-6, TGF-β1, TGF-β2, TGF-β3 and a reduced level of IL-5, IL-13 compared to PRS without comorbid pathology. Conclusions. Given the same clinical course of polypous rhinosinusitis, the identification of the difference in the cytokine profile in the nasal polyp tissue gives evidence of a different mechanism of the inflammatory response for different phenotypes of PRS. The polypous rhinosinusitis combined with allergic rhinitis is characterized by 100% eosinophilic type of inflammation, high levels of TGF-β family protein cytokines, pro-inflammatory cytokine IL-6 and a lower level of T2-cytokines IL-5 and IL-13 compared with the PRS group without comorbid pathology. The simultaneous treatment of PRS and allergic rhinitis using the joint efforts of otorhinolaryngologists and allergists will allow to achieve medical monitoring of both diseases and prevent their progression and development of complications.

Immunologic Features of Patients With Advanced Hepatocellular Carcinoma Before and During Sorafenib or Anti-programmed Death-1/Programmed Death-L1 Treatment.

INTRODUCTION:Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. Today, a promising treatment strategy is focused on the enhancement of antitumor immune responses by immune checkpoint modification. However, as only 20% of patients with HCC are responders, identification of predictive factors is urgently required. Therefore, for the first time, the features of the intrahepatic and circulating immune system in patients with advanced-stage HCC, before and during the treatment, were analyzed.METHODS:We collected fresh HCC biopsies, along with adjacent tumor-free liver tissues and peripheral blood samples, from 21 patients with advanced HCC. Furthermore, we performed an extensive immunomonitoring of patients with HCC treated with sorafenib or programmed death (PD)-1/PD-L1 pathway blockade using multiparametric flow cytometry.RESULTS:We observed that regardless of the treatment, low baseline intratumoral CD4+/CD8+ T-cell ratio was associated with better overall survival (P = 0.0002). The baseline frequency of intratumoral PD-1high CD8+ T cells was significantly lower in patients responding to sorafenib treatment than in the nonresponders (P = 0.0117), and the frequency of circulating PD-1high T cells increased with tumor progression (P = 0.0329). By contrast, responders to PD-1/PD-L1 pathway blockade showed a trend of high baseline frequency of intratumoral PD-1high CD8+ T cells. Moreover, we observed a trend of LAG3 and TIM3 upregulation on circulating T cells in nonresponding patients to PD-1/PD-L1 pathway blockade.DISCUSSION:Immunosuppressive state, characterized by an enhanced intratumoral CD4+/CD8+ T-cell ratio, was associated with poor prognosis. Additionally, our results suggest that the frequency of intratumoral PD-1high CD8+ T cells may serve as a biomarker to identify which individuals will benefit from which treatment and support the use of combination strategies.

Serum cytokines and clinical features in patients with fever and thrombocytopenia syndrome

PurposeTo explore the clinical, microbiological and immunological features of patients with fever and thrombocytopenia. MethodsPatients with unexplained fever and thrombocytopenia were enrolled. Viruses were detected using real-time PCR, and bacteria were measured by culturing methods. Serum cytokines, platelet antibody IgG (PA-IgG) and Helicobacter pylori (HP) were detected using ELISA. ResultsPathogens were detected in 74.68% of patients, which included single fungal/viral/bacterial infection and multiple infection. The pathogens could not be unidentified in 25.32% of cases. Cytokines including Interleukin (IL)-6, IL-10, interferon-γ(IFN-γ), platelet activating factor (PAF) and PA-IgG were significantly higher in patients as compared to healthy controls (P < .01 or P < .05). Principal component analyses extracted four groups of parameters that have a strong positive predicting value, revealing that disease status evaluation would be more accurate if we combined the platelet parameters and inflammatory biomarkers. While event-free survival (EFS) that indicates the time of platelet elevated after therapy was the highest in patients with single bacterial or fungal infection, EFS was affected by the levels of cytokines and PA-IgG. ConclusionsDifferences in immune function may be the main factors affecting the prognosis of patients with fever and thrombocytopenia, while treatment based on precise etiological diagnosis is important for therapeutic efficacy.

Quantitative clinical and autoimmune assessments in stiff person syndrome: evidence for a progressive disorder

BackgroundStiff Person Syndrome (SPS) is an under-diagnosed disorder that affects mobility and the quality of life of affected patients. The aim of the study is to describe the natural history of SPS, the extent of accumulated disability and the associated clinical and immunological features in patients followed for up to 8 years in a single center.MethodsOur collective cohort included 57 SPS patients. Additionally, 32 of these patients were examined every 6 months for a two-year period in a longitudinal study protocol, to assess disease progression using quantitative measures of stiffness and heightened sensitivity.ResultsThe most frequent initial symptom was leg stiffness, followed by paraspinal muscle rigidity and painful spasms in 95% of the patients. Although none of the patients required assistance for ambulation during the first 2 years of disease onset, 46 patients (80%) lost the ability to walk independently during our follow-up, despite symptomatic medications. In the longitudinal cohort, the number of stiff areas increased (p < 0.0001), consistent with worsening functional status and quality of life. High-titer anti-GAD antibodies were present in serum and CSF with elevated intrathecal GAD-specific IgG synthesis, but they did not correlate with clinical severity or progression.ConclusionsThis large study on SPS patients, combining an eight-year follow-up at a single center by the same leading neurologist and his team, is the first to provide longitudinal data in a large patient subgroup using objective clinical measures. One of the main findings is that SPS is a progressive disease leading to physical disability over time.

Clinical and immunophenotypic characteristics of patients with chromosome 22q11.2 deletion syndrome: a single institution's experience.

Aim:The aim of this study was to identify the clinical and immunologic features of patients with 22q11.2 deletion syndrome who were followed up in our clinic. Thus, it is aimed to identify the syndrome early, choose the right treatment options according to humoral and cellular immunologic analysis, and enlighten how to follow up these kinds of patients with immunodeficiencies.Material and Methods:We retrospectively collected data by reviewing the files of 11 patients with 22q11.2 deletion syndrome who were followed up in our clinic between January 2003 and January 2015. The diagnoses were based on the patients’ clinical, genetic, and immunologic features. Demographic features, family history, initial symptoms on admission, physical findings, and results of immunologic studies of the patients. Age of diagnosis, treatment options, and clinical follow-up were evaluated.Results:The patients’ diagnosis age ranged from 1-11 months and the most common symptoms of admission were cardiac murmur and atypical facial appearance, which were detected during a routine physical examination. All patients had cardiac anomalies, and four patients had a history of cardiovascular surgery. Eight patients (72.7%) had a history of severe infection; recurrent lower respiratory tract infections were reported in six patients (54.5%), pulmonary tuberculosis in one patient (9.1%), and moniliasis resistant to treatment was detected in one patient. None of the patients required intravenous immunoglobulin replacement therapy, and antibiotic prophylaxis was administered to two patients with lymphopenia.Conclusion:22q11.2 deletion syndrome is a multi-systemic disorder that should be evaluated by a multidisciplinary team. It should be kept in mind for patients with neonatal hypocalcemic tetany or recurrent infections or atypical facial appearance with cardiac anomalies. Early diagnosis should lead to immunologic analysis and enable the choice of treatment. Preventive measures against infection is recommended for the patients with incomplete immunodeficiency, and thymus transplantation is recommended for patients with complete immunodeficiency.

PREDICTION OF TOCILIZUMAB AND RITUXIMAB EFFECTIVENESS IN RHEUMATOID ARTHRITIS

Objective: to study the possibility of prediction of treatment effectiveness with tocilizumab and rituximab in rheumatoid arthritis (RA), taking into account the clinical and immunological characteristics of patients. Material and methods. The efficacy of treatment with tocilizumab in 53 patients and rituximab in 22 patients with RA within 12 months was analyzed, the prognostic role of the initial values of activity indices, the presence of systemic manifestations, the duration of RA, levels of autoantibodies and acute phase proteins was evaluated. Results. The high efficacy of treatment with biological drugs in RA was established, the treatment goals were achieved by 84.91% of patients in the group of tocilizumab and 72.72% in the group of rituximab, but the remaining patients did not reach the treatment goal after 12 months of follow-up. Conclusions. Reliable predictors of a good response to tocilizumab in RA may be high activity of the joint syndrome, rituximab – seropositive variant of RA, as well as the presence of systemic manifestations.

Clinico-laboratory and immunological characteristics of patients with compensated cirrhosis of the liver in the outcome of chronic hepatitis C on the background of treatment with a direct antiviral drug paritrapeprir/ritonavir/ombitasvir/ dasabuvir

Goal. Paritrapeprir / ritonavir / ombitasvir / dasabuvir on the clinical and laboratory parameters, including thesubpopulation composition of lymphocytes, in patients with compensated cirrhosis in the outcome of chronic hepatitis C. Materials and methods. The study included patients with compensated liver cirrhosis class A (no more than 6 on the Child – Turcotte – Pugh scale), in the outcome of chronic hepatitis C, genotype 1b (group 1, n = 28). The comparison group (group 2, n = 25) consisted of patients comparable in terms of gender and main study parameters, not receiving antiviral therapy. Results. A stable virologic response was 96,8%. There were no serious adverse events requiring treatment reversal. As a result of treatment, there was a disappearance or a significant decrease in the severity of asthenovegetative and dyspeptic syndromes, a reduction in liver size, an improvement in liver functional parameters (biochemical response), and normalization of the balance of the cellular immunity by increasing CD3 +, CD4 +, CD8 + – CD16 + lymphocyte counts. The conclusion. Etiotropic therapy with paritrapeprir /ritonavir / ombitasvir / dasabuvir is well tolerated by patients with compensated cirrhosis in the outcome of chronic hepatitis C, has high efficacy, positively influences the dynamics of clinical manifestations, and also helps reduce the imbalance of the cellular immunity.

Clinical and immunological characteristics of patients with chronic hepatitis C during antiviral therapy in interferon-free regimen

Aim. To study the biomarkers of liver inflammation that occur during antiviral therapy in the interferon-free regimen.&#x0D; Methods. 14 patients were examined during antiviral therapy of chronic viral hepatitis C genotype 1. Treatment with dasabuvir, ombitasvir, paritaprevir and ritonavir for 12 weeks was received by 8 patients. Daklatasvir and asunaprevir was administered to 6 patients for 24 weeks. 11 patients had the concentrations of cytokines/chemokines (TNFα, CCL2/MCP-1, CCL20/MIP-3α, CXCL9/MIG, CXCL10/IP-10, CXCL11/ITAC) measured in the blood plasma by multiplex analysis. In six patients, the content of CXCR3+ and CCR6+ receptors in different subpopulations of lymphocytes was determined by flow cytofluorimetry. Patients were divided into 2 groups: without liver fibrosis and with severe fibrosis.&#x0D; Results. 100% demonstrated virologic response. In both groups, significant reduction of CXCL10/IP-10 concentration was found in the patients at the end of treatment compared to pre-therapy (p=0.025 and 0.00015, respectively). In the first group a tendency to increase of the relative content of T-lymphocytes (p=0.065) was observed, and in the second group, a significant increase of the relative content of TNKCCR6+ (p=0.02) was observed.&#x0D; Conclusion. Chemokine CXCL10/IP-10 is a biomarker characterizing the decrease of liver inflammation during therapy and not depending on the degree of liver fibrosis. The tendency to increase of the relative content of T lymphocytes in the first group and a significant increase in TNKCCR6+ cells during treatment in the second group may play an important role in eliminating hepatitis C virus.

Phenotyping and long-term follow up of patients with hyper IgE syndrome

Introduction and objectivesLong-term follow up of patients with hyper IgE syndrome (HIES), as a primary immunodeficiency disorder, has been poorly investigated. This study describes common clinical and immunological features of patients with HIES in the last 10 years in Shiraz University of Medical Sciences, Shiraz, Iran. Methods and patientsIn this cross-sectional study, the symptoms and medical records of 18 patients, who were diagnosed with HIES, were observed. Genetic and immunologic study was also performed. ResultsEighteen patients with the mean age of 13 years old were investigated. Ten patients were detected to have mutations in DOCK8 gene and autosomal recessive HIES (AR-HIES); and four patients were found with STAT3 mutation and autosomal dominant HIES (AD-HIES). So, 14 patients with known genetic results were considered for further data analysis. Food allergy, eczema, viral and skin infections were the major complications of AR-HIES patients. The major clinical complications of AD-HIES patients were pneumonia, skin infections and eczema. Food allergy and viral infection were significantly higher in DOCK8 deficient patients. The most common causes of hospitalization in both AR-HIES and AD-HIES patients were pneumonia, skin infections and sepsis. The most common cause of death was found to be sepsis. ConclusionsAD-HIES and AR-HIES cannot be differentiated only based on the clinical presentations. Genetic features are also necessary for better diagnosis. This study, summarizing the clinical, immunological and genetic information of the patients with AD-HIES and AR-HIES, may open a way for better diagnosis and management of HIES.

Increased risk of severe course of pemphigus in patients with pemphigus-associated alopecia: a prospective observational study.

Pemphigus-associated alopecia is considered rare, and has not been studied in detail. To evaluate the clinical and immunological characteristics of patients with pemphigus-associated alopecia. This prospective observational study included 80 consecutive patients with histopathologically and immunopathologically confirmed pemphigus, of whom 11 (13.8%) were found to have pemphigus-associated alopecia. Alopecia was observed in 11/52 patients with pemphigus and scalp involvement: [0/28 (35.7%) with pemphigus vulgaris and 1/24 (4.2%) with pemphigus foliaceus. The clinical and immunological characteristics of these patients were analysed. Patients with pemphigus-associated alopecia had a significantly higher Pemphigus Disease Area Index total activity score compared with patients who had no pemphigus-associated alopecia (21.8 ± 18.6 and 11.0 ± 20.5, respectively; P = 0.02). Mean serum anti-desmoglein (Dsg)1 antibody concentration was 141.8 ± 66.9 U/mL and 60.0 ± 52.6 U/mL, respectively (P = 0.03), and mean serum anti-Dsg3 concentration was 126.6 ± 36.7 U/mL and 67.4 ± 52.5 U/mL, respectively (P = 0.03). The values for achieving serological remission were 10% and 70%, respectively (P = 0.02). Pemphigus-associated alopecia is a marker of severe disease and a treatment-resistant disease course.

Treatment of Granulomas in Patients With Ataxia Telangiectasia.

Background: Ataxia telangiectasia (A-T) is a devastating multi-system disorder characterized by progressive cerebellar ataxia, growth retardation, immunodeficiency, chronic pulmonary disease and chromosomal instability. Cutaneous granulomas are a known phenomenon in A-T but extra-dermal manifestation of granulomas at bone and synovia has not been reported so far. The clinical presentation, immunological findings, the long-term course and treatment options of eight patients with severe granulomas will be reported.Methods: From our cohort of 44 classical A-T patients, eight patients aged 2–11 years (18.2%) presented with granulomas. Immunological features of patients with and without granulomas were compared. Five patients suffered from cutaneous manifestation, in two patients we detected a bone and in one a joint involvement. Patients with significant extra-dermal involvement as well as one patient with massive skin manifestation were treated with TNF inhibitors. The patient with granulomas at his finger joint and elbow was treated with hematopoietic stem cell transplantation (HSCT).Results: Interestingly, seven of eight patients with granulomas were total IgA deficient, but there were no differences in IgG and IgM levels. All lymphocytes subsets were equally distributed except patients with granuloma had significantly lower naïve CD8 cells. In patients without treatment, four of eight showed a slow but significant enlargement of the granuloma. Treatment success with TNF inhibitors was variable. In one patient, treatment with TNF inhibitors led to a total remission for 3 years up to now. In two patients, treatment with TNF inhibitors led to a partial regression of granulomas. Treatment interruptions caused deterioration again.Conclusions: Granulomas in A-T progress slowly over years and can lead to significant morbidity.Treatment with TNF inhibitors was safe and in part successful in our patients. Interestingly HSCT leads to complete remission, and indicates that aberrant immune function is responsible for granulomas in A-T patients. What This Study Adds to the Field: Granulomas in A-T progress slowly over years and can lead to significant morbidity. Treatment with TNF inhibitors was safe and in part successful in our patients.AT A GLANCE COMMENTARY:Scientific knowledge on the subject: Little is known about the clinical presentation, course and treatment of granulomas in ataxia telangiectasia (A-T). In addition, this is the first report of extra-dermal manifestation of granulomas at bone and synovia in patients with A-T.What This Study Adds to the Field: Granulomas in A-T progress slowly over years and can lead to significant morbidity. Treatment with TNF inhibitors was safe and in part successful in our patients.

The Clinical and Immunological Features of Patients with Primary Antibody Deficiencies.

Primary antibody deficiency (PAD) comprises a range of diseases from early to late terminal B cells defects and is associated with the various clinical complications. A total of 461 patients (311 males and 150 females) with PADs enrolled in the retrospective cohort study and for all patients' demographic information, clinical records and laboratory data were collected to investigate clinical complications. The most prevalent first presentations of immunodeficiency were respiratory tract infections in 63.5% and chronic diarrhea in 17.2%. Common variable immune deficiency (CVID) patients had a higher diagnostic delay than class switching defect (CSD), and agammaglobulinemia. Among the noninfectious complications, autoimmunity (26.2%), and splenomegaly (23.4%) were the most common. Lymphadenopathy was higher in CSD patients than other PADs, while splenomegaly, hepatomegaly, autoimmunity and bronchiectasis were more common in CVID patients than others. Atopic manifestations were mostly recorded in patients with selective IgA deficiency. Malignancy was only reported in 5.8% of patients with CVID. There was a higher prevalence of autoimmune manifestations in CVID comparing to other PADs. PADs are relatively rare diseases and these patients have a variety of first clinical manifestations, such as diverse infections, autoimmunity, lymphoproliferation, allergy, enteropathy and malignancy. Practitioner's awareness about the heterogeneous presentations of PAD disorders is poor, therefore patients often are lately diagnosed, and they are complicated with several clinical complications before the certain diagnosis.