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Background: Patients with loss of function signal transducer and activator of transcription 3-related Hyper IgE Syndrome (LOF STAT3 HIES) present with recurrent staphylococcal skin and pulmonary infections along with the elevated serum IgE levels, eczematous rashes, and skeletal and facial abnormalities. Defective STAT3 signaling results in reduced Th17 cells and an impaired IL-17/IL-22 response primarily due to a compromised canonical Janus kinase-signal transducer and activator of transcription (JAK–STAT) pathway that involves STAT3 phosphorylation, dimerization, nuclear translocation, and gene transcription. The non-canonical pathway involving unphosphorylated STAT3 and its role in disease pathogenesis, however, is unexplored in HIES. Objective: This study aims to elucidate the role of unphosphorylated STAT3–unphosphorylated NF-kB (uSTAT3–uNF-kB) activation pathway in LOF STAT3 HIES patients. Methodology: The mRNA expression of downstream molecules of unphosphorylated STAT3–unphosphorylated NF-kB pathway was studied in five LOF STAT3 HIES patients and transfected STAT3 mutants post-IL-6 stimulation. Immunoprecipitation assays were performed to assess the binding of STAT3 and NF-kB to RANTES promoter. Results: A reduced expression of the downstream signaling molecules of the uSTAT3–uNF-kB complex pathway, viz., RANTES, STAT3, IL-6, IL-8, ICAM1, IL-8, ZFP36L2, CSF1, MRAS, and SOCS3, in LOF STAT3 HIES patients as well as the different STAT3 mutant plasmids was observed. Immunoprecipitation studies showed a reduced interaction of STAT3 and NF-kB to RANTES in HIES patients. Conclusion: The reduced expression of downstream signaling molecules, specially RANTES and STAT3, confirmed the impaired uSTAT3–uNF-kB pathway in STAT3 LOF HIES. Decreased levels of RANTES and STAT3 could be a significant component in the disease pathogenesis of Hyper IgE Syndrome. [ABSTRACT FROM AUTHOR]

Background: Human leukocyte antigen (HLA) allele frequencies have a known association with the pathogenesis of various autoimmune diseases. Methods: We recruited 31 Indian patients of acquired dermal macular hyperpigmentation (ADMH) and 60 unrelated, age‐and‐gender‐matched healthy controls. After history and clinical examination, 5 ml of blood in EDTA vials was collected. These samples were subjected to DNA extraction and the expression of HLA A, B, C, DR, DQ‐A, and DQ‐B was studied. Results: There was a predominance of females with a gender ratio of 23 : 8 and the most common phototype was Fitzpatrick type IV (83.9%). There was a significant association of HLA A*03:01 (OR: 5.8, CI: 1.7–17.0, P = 0.005), HLA B*07:02 (OR: 5.3, CI: 1.9–14.6, P = 0.003), HLA C*07:02 (OR: 4.3, CI: 1.8–9.6, P = 0.001), HLA DRB1*10:01 (OR: 7.6, CI: 1.7–38.00, P = 0.022), and HLA DRB1*15:02 (OR: 31.0, CI: 4.4–341.8, P < 0.001) with patients compared to controls, whereas HLA DQB*03:01 was less associated with patients compared to controls (OR: 0.2, CI: 0.0–0.6, P = 0.009). Conclusion: Patients with ADMH are more likely to have the HLA A*03:01, HLA B 07*02, HLA C*07:02, HLA DRB1*10:01, HLA DRB1*15:02 and less likely to have the HLA DQB*03:01 allele. Larger cohort studies may thus be conducted studying these specific alleles. [ABSTRACT FROM AUTHOR]

Objective: Multisystem inflammatory syndrome (MIS-C) in children is a febrile illness that has overlapping presentation with other locally prevalent illnesses. Clinicolaboratory profile of children admitted with MIS-C and dengue were compared to understand their presentation at the outset. Methods: This was a retrospective study of children ≤ 12 y admitted with MIS-C (WHO definition) or laboratory-confirmed dengue between August 2020 and January 2021 at a tertiary center in North India. Results: A total of 84 children (MIS-C - 40; dengue - 44) were included. The mean (SD) age [83.5 (39) vs. 91.6 (35) mo] was comparable. Rash (72.5% vs. 22.7%), conjunctival injection (60% vs. 2.3%), oral mucocutaneous changes (27.5% vs. 0) and gallop rhythm (15% vs. 0) were seen more frequently with MIS-C, while petechiae [29.5% vs. 7.5%], myalgia (38.6% vs. 10%), headache (22.7% vs. 2.5%), and hepatomegaly (68.2% vs. 27.5%) were more common with dengue. Children with MIS-C had significantly higher C-reactive protein (124 vs. 3.2 mg/L) and interleukin 6 (95.3 vs. 20.7 ng/mL), while those with dengue had higher hemoglobin (12 vs. 10.2 g/dL) lower mean platelet count (26 vs. 140 × 109/L), and greater elevation in aspartate (607 vs. 44 IU/L) and alanine (235.5 vs. 56 IU/L) aminotransferases. The hospital stay was longer with MIS-C; however, PICU stay and mortality were comparable. Conclusion: In hospitalized children with acute febrile illness, the presence of mucocutaneous features and highly elevated CRP could distinguish MIS-C from dengue. The presence of petechiae, hepatomegaly, and hemoconcentration may favor a diagnosis of dengue. [ABSTRACT FROM AUTHOR]

Background: Information on bullous pemphigoid in an Indian context is scarce. Aim: To report clinico-demographic profile, associated comorbidities and prescription pattern of bullous pemphigoid patients in India. Methods: This was a retrospective study, where past records of all bullous pemphigoid patients diagnosed and treated between November 2013 and October 2019 were accessed and analysed. Patients having a compatible clinical presentation with either histopathological and/or direct immunofluorescence evidence of bullous pemphigoid were included. Results: There were 96 bullous pemphigoid patients, with a male: female ratio of 1.6:1. The mean age at diagnosis was 62.5 ± 2.2 years, with mean duration of illness 27.5 ± 4.5 months before presentation. Comorbidities were present in 80 (83%) patients, with type 2 diabetes mellitus (38.5%), hypertension (36.4%) and neurological illness (16.7%) being the commonest ones. Clinically, blisters were the predominant presentation in 81 (84.4%) patients. The majority (87.5%) of patients showed a predominant eosinophilic infiltrate on histopathology. Direct immunofluorescence revealed immunoglobulin G deposits with complement C3 in 77 (80.2%) cases. The majority of patients (77.1%) were treated with oral prednisolone, either alone (11.5%) or in combination (65.6%) with other topical and systemic agents. Topical steroids were used in 29.1%, azathioprine in 28%, dapsone in 16.7% and omalizumab in 6.2% of patients. Limitations: The study is retrospective. Immunofluorescence on salt split skin, direct immunofluorescence serration pattern analysis, and immunoblotting were not performed. Hence, there is a possibility that a few included cases were suffering from other subepidermal autoimmune bullous diseases like epidermolysis bullosa acquisita or anti-p200 pemphigoid. Conclusion: Bullous pemphigoid patients in this study had a younger age of onset and showed male preponderance. Comorbidities like type 2 diabetes, hypertension and neurological disorders were frequent. Cutaneous blisters were the most frequent clinical presentation. Systemic corticosteroids comprised the mainstay of therapy. [ABSTRACT FROM AUTHOR]

Aim: Considering Acute and Transient psychotic disorders (ATPDs) to be a close entity to Schizophrenia (SZ) with a completely different course and outcome, studies evaluating the immunological abnormalities are scarce in ATPDs. We analysed immune‐mediated inflammatory marker levels [Interleukin‐2 (IL‐2), Interleukin‐4 (IL‐4), Interleukin‐6 (IL‐6), Interleukin‐8 (IL‐8), Interleukin‐17 (IL‐17) and Tumour necrosis factor‐alpha (TNF‐α)] in patients with ATPDs (in the acute phase and after remission), and compared these with patients with SZ in remission and with healthy controls. Methods: Ninteen subjects with ATPDs in acute phase of illness were age−/gender‐matched with healthy controls and patients with schizophrenia in remission; recruited through purposive sampling. Clinical assessment and immune‐marker levels were carried out in all the three groups. Follow –up repeat immune‐marker levels assessment in the ATPD group was conducted after remission status was ensured. Immune‐marker levels were compared across the three groups. Results: Patients with ATPDs had elevated levels of the pro‐inflammatory cytokines IL‐6 and IL‐17 and low levels of IL‐8 in the acute phase and low levels of IL‐6 and elevated levels of IL‐8 during the remission phase. Compared to patients with SZ in remission, patients with ATPD in remission had low levels of all the three pro‐inflammatory cytokines (with significantly low IL‐6 levels and non‐significant, yet low levels of IL‐8 and IL‐17) and had significantly low and high levels of IL‐6 and IL‐8 respectively than healthy controls. Conclusion: These findings suggest that there existed immunological abnormalities in the acute and remission phase of illness in patients with ATPDs compared to both patients with SZ in remission and healthy controls. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal tuberculosis (GITB) and Crohn's disease (CD) are close mimickers and difficult to discriminate. Recent work has focused on the immunological differences between GITB and CD based on cytokines related to T-regulatory cells and Th17 cells. In the present cross-sectional study, suspected cases of GITB or CD underwent extensive clinical, radiological, endoscopic, histological, and microbiological assessment. The diagnosis was based on standard criteria and response to antitubercular therapy endoscopically. Methods: Interleukin (IL)-10, transforming growth factor-ß (TGF-ß), and IL-17 were measured and compared between GITB and CD along with other parameters. Fisher's exact test and Mann-Whitney U test were used as per the data type. Results: Of the 27 patients, 11 had CD, 9 had GITB, and 7 had other conditions. Chronic diarrhea, involvement of left and long segments of the colon, and aphthous ulcers were significantly more frequent in CD; however, transverse ulcers were in GITB. IL-10 was reduced in both GITB (median-interquartile range [IQR] 9.54 [3.65-24.04]) and CD (median-IQR 13.28 [6.91-22.50]) compared to control (median-IQR 26.72 [10.34-35.43]). TGF-ß showed little variation, but IL-17 was below the detection limit in most cases. None of these cytokines were significantly different between CD and GITB. The sensitivity and specificity of multiplex Mycobacterium tuberculosis-polymerase chain reaction were 44.44% and 100%, respectively. Conclusion: Serum cytokine profiling (IL-10, IL-17, and TGF-ß) could not significantly differentiate GITB and CD. Moreover, extensive molecular, transcriptomic, chemokines, and cytokine analyses may shed light on these aspects. [ABSTRACT FROM AUTHOR]