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1.
Heliyon ; 10(7): e25732, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38601584

ABSTRACT

Transformations of applied phosphorus (P) fertilizer to inaccessible residual soil P is the main cause of inadequate P availability to plants in the majority of the cultivated soils. This study investigated the effect of organic wastes (rice-residue biochar, farmyard manure (FYM), poultry manure (PM), green manure (GM), and wheat straw (WS) on residual-P mobilization and its bioavailability in maize crops under different P status soils. Surface soil samples of 'medium-P' (12.5-22.5 kg P ha-1) and 'high-P' (22.5-50.0 kg P ha-1) status soils were collected from a long-term differential P fertilization experiment on maize-wheat rotation and were subjected to examine P adsorption/desorption, phosphatase activity and microbial biomass P (MBP) after incubation with organic amendments of varying elemental composition. The incorporation of organic manures decreases P sorption with maximum decrease in FYM-treated soils, indicating increased P concentration in soil solution. In contrast, WS due to its wider C/P ratio increased P sorption and did not produce any significant impact on the bioavailability of P. High-P status soils witnessed lower P sorption than medium-P soils. The MBP increased in the order of PM > FYM > GM > WS > biochar irrespective of soil P status. The availability and mobility of residual-P with FYM and PM was significantly higher than that of residual-P from biochar, GM and WS. Organics with wider C/P ratio immobilize bioavailable P in the short term regardless of soil P status.

2.
Biochem Genet ; 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38605207

ABSTRACT

Esophageal cancer is the eighth most common cancer worldwide and fourth most common in developing countries. Altered glycosylation pattern of cell membrane molecules along with inflammation is a characteristic attribute of oncogenesis. Galectin-4, a tandem repeat galectin, has shown effect on cancer progression/metastasis in digestive system cancers. This role of galectin-4 can be attributed to variations in LGALS4, gene encoding galectin-4. The present case-control study was designed to analyze four intronic SNPs in LGALS4 with susceptibility toward esophageal cancer.Esophageal cancer cases and age- and gender-matched apparently healthy individuals were recruited for the present study. Genotyping of rs8113319, rs4802886, rs4802887, and rs12610990 was carried out using Sanger sequencing and PCR-RFLP. MedCalc software, SNPStats and SHEsis online platform were used for statistical analysis.Genotypic analyses revealed an overall increased heterozygosity of rs12610990, rs4802886, and rs4802887, and AA genotype of rs8113319 in the study participants. Haplotypic analyses also revealed a predominance of AAAT haplotype in the cases. Moreover, combined presence of wild alleles of rs4802886 and rs4802887 could influence protection toward disease, and combined presence of wild alleles of rs12610990 and rs8113319 could influence disease susceptibility. Furthermore, a strong linkage disequilibrium was also observed between the SNPs. Further studies are underway to validate galectin-4 and its genetic variants as blood-based biomarkers in early disease diagnosis, improving treatment outcome.

3.
Acta Diabetol ; 61(6): 791-805, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38483572

ABSTRACT

AIM: This study was undertaken to explicate the shared and distinctive genetic susceptibility and immune dysfunction in patients with T1D alone and T1D with CD (T1D + CD). METHODS: A total of 100 T1D, 50 T1D + CD and 150 healthy controls were recruited. HLA-DRB1/DQB1 alleles were determined by PCR-sequence-specific primer method, SNP genotyping for CTLA-4 and PTPN22 was done by simple probe-based SNP-array and genotyping for INS-23 Hph1 A/T was done by RFLP. Autoantibodies and cytokine estimation was done by ELISA. Immune-regulation was analysed by flow-cytometry. Clustering of autoantigen epitopes was done by epitope cluster analytical tool. RESULTS: Both T1D alone and T1D + CD had a shared association of DRB1*03:01, DRB1*04, DRB3*01:07/15 and DQB1*02. DRB3*01:07/15 confers the highest risk for T1D with relative risk of 11.32 (5.74-22.31). Non-HLA gene polymorphisms PTPN22 and INS could discriminate between T1D and T1D + CD. T1D + CD have significantly higher titers of autoantibodies, expression of costimulatory molecules on CD4 and CD8 cells, and cytokine IL-17A and TGF-ß1 levels compared to T1D patients. Epitopes from immunodominant regions of autoantigens of T1D and CD clustered together with 40% homology. CONCLUSION: Same HLA genes provide susceptibility for both T1D and CD. Non-HLA genes CTLA4, PTPN22 and INS provide further susceptibility while different polymorphisms in PTPN22 and INS can discriminate between T1D and T1D + CD. Epitope homology between autoantigens of two diseases further encourages the two diseases to occur together. The T1D + CD being more common in females along with co-existence of thyroid autoimmunity, and have more immune dysregulated state than T1D alone.


Subject(s)
Autoantigens , Celiac Disease , Diabetes Mellitus, Type 1 , Genetic Predisposition to Disease , Protein Tyrosine Phosphatase, Non-Receptor Type 22 , Humans , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/immunology , India/epidemiology , Celiac Disease/genetics , Celiac Disease/immunology , Female , Male , Autoantigens/immunology , Autoantigens/genetics , Child , Adolescent , Protein Tyrosine Phosphatase, Non-Receptor Type 22/genetics , Adult , HLA-DQ beta-Chains/genetics , Autoantibodies/immunology , Autoantibodies/blood , HLA-DRB1 Chains/genetics , Young Adult , Polymorphism, Single Nucleotide , Child, Preschool , CTLA-4 Antigen/genetics , Genotype , Case-Control Studies
4.
Heliyon ; 10(3): e25896, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38356557

ABSTRACT

During the pandemic, artificial intelligence was employed and utilized by students around the globe. Students' conduct changed in a variety of ways when schooling returned to regular instruction. This study aimed to analyze the student's behavioral intention and actual academic use of communicational AI (CAI) as an educational tool. This study identified the variables by utilizing an integrated framework based on the Unified Theory of Acceptance and Use of Technology (UTAUT2) and self-determination theory. Through the use of an online survey and Structural Equation Modeling, data from 533 respondents were analyzed. The results showed that perceived relatedness has the most significant effect on the behavioral intention of students in using CAI as an educational tool, followed by perceived autonomy. It showed that students use CAI based on the objective and the possibility of increasing their productivity, rather than any other purpose in the education setting. Among the UTAUT2 domains, only facilitating conditions, habit, and performance expectancy provided a significant direct effect on behavioral intention and an indirect effect on actual academic use. Further implications were presented. Moreover, the methodology and framework of this study could be extended and applied to educational technology-related studies. Lastly, the outcome of this study may be considered in analyzing the behavioral intention of the students as the teaching-learning environment is still continuously expanding and developing.

5.
Circ Heart Fail ; 17(1): e011105, 2024 01.
Article in English | MEDLINE | ID: mdl-38179728

ABSTRACT

BACKGROUND: The use of urinary sodium to guide diuretics in acute heart failure is recommended by experts and the most recent European Society of Cardiology guidelines. However, there are limited data to support this recommendation. The ENACT-HF study (Efficacy of a Standardized Diuretic Protocol in Acute Heart Failure) investigated the feasibility and efficacy of a standardized natriuresis-guided diuretic protocol in patients with acute heart failure and signs of volume overload. METHODS: ENACT-HF was an international, multicenter, open-label, pragmatic, 2-phase study, comparing the current standard of care of each center with a standardized diuretic protocol, including urinary sodium to guide therapy. The primary end point was natriuresis after 1 day. Secondary end points included cumulative natriuresis and diuresis after 2 days of treatment, length of stay, and in-hospital mortality. All end points were adjusted for baseline differences between both treatment arms. RESULTS: Four hundred one patients from 29 centers in 18 countries worldwide were included in the study. The natriuresis after 1 day was significantly higher in the protocol arm compared with the standard of care arm (282 versus 174 mmol; adjusted mean ratio, 1.64; P<0.001). After 2 days, the natriuresis remained higher in the protocol arm (538 versus 365 mmol; adjusted mean ratio, 1.52; P<0.001), with a significantly higher diuresis (5776 versus 4381 mL; adjusted mean ratio, 1.33; P<0.001). The protocol arm had a shorter length of stay (5.8 versus 7.0 days; adjusted mean ratio, 0.87; P=0.036). In-hospital mortality was low and did not significantly differ between the 2 arms (1.4% versus 2.0%; P=0.852). CONCLUSIONS: A standardized natriuresis-guided diuretic protocol to guide decongestion in acute heart failure was feasible, safe, and resulted in higher natriuresis and diuresis, as well as a shorter length of stay.


Subject(s)
Diuretics , Heart Failure , Humans , Diuretics/therapeutic use , Natriuresis , Heart Failure/diagnosis , Heart Failure/drug therapy , Diuresis , Sodium , Sodium Potassium Chloride Symporter Inhibitors/adverse effects
6.
Int J Dermatol ; 63(6): 773-779, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38263574

ABSTRACT

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.


Subject(s)
Gene Frequency , HLA-DQ beta-Chains , Hyperpigmentation , Humans , Female , Male , Case-Control Studies , Hyperpigmentation/genetics , Hyperpigmentation/immunology , Adult , HLA-DQ beta-Chains/genetics , HLA-DRB1 Chains/genetics , Middle Aged , HLA-A Antigens/genetics , Young Adult , HLA-B Antigens/genetics , HLA-C Antigens/genetics , India/epidemiology , HLA-DR Antigens/genetics , HLA-B7 Antigen/genetics , HLA-DQ alpha-Chains/genetics , Adolescent , HLA Antigens/genetics , HLA Antigens/immunology
8.
J Orthop Case Rep ; 13(11): 142-146, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38025348

ABSTRACT

Introduction: High-energy trauma has increased the incidence of traumatic hip dislocation and dislocation is often associated with fractures. However, a hip fracture-dislocation extending to the ipsilateral femoral trochanter is exceedingly rare and only a few cases have been described. We report a case of irreducible posterior dislocation of the hip with ipsilateral intertrochanteric fracture managed by open reduction and osteosynthesis. Case Report: A 50-year-old male presented with a history of fall from an electricity pole with pain in the left hip and an inability to bear weight on his left lower limb. Radiographs confirmed the presence of posterior dislocation of the left hip with comminuted intertrochanteric fracture on the same side. Conclusion: Posterior dislocation of the hip with same side inter trochanteric fracture is a rare traumatic entity, with only few case being reported. Literature does not provide any classification for such rare traumatic fracture dislocation. Management of such fracture requires early diagnosis and intervention which can result in good prognosis.

9.
J Orthop Case Rep ; 13(11): 171-179, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38025361

ABSTRACT

Introduction: Giant cell tumor (GCT) represents 5% of all primary bone tumors and 20% of biopsy analyzed benign tumors. More than half of these lesions occur in the 3rd and 4th decades of life. There is no absolute treatment method selection. Techniques ranging from intralesional curettage to wide resection can be used. Goal is to eradicate the tumor, preserve limb function, and prevent local recurrence and distant metastasis. Case Report: We are presenting seven cases of GCT at five different and rare sites involving tibia, calcaneum, metatarsal, proximal humerus, and clavicle with tumor being limited to bone in all seven cases not involving the soft tissue. There were three male patients and four female patients. Six patients underwent intralesional curettage using high-speed burr and curette, along with adjuvant irrigation with hydrogen peroxide and normal saline followed by polymethyl methacrylate reconstruction. One patient with GCT clavicle underwent wide resection. Results: In all seven cases, we were able to able to remove the tumor completely. Six patients had a gradual and complete recovery with return to near normal activity within 6 month-1 year after surgery. One patient with proximal humerus GCT had a recurrence which got resolved with injection denosumab. All patients have been followed up for a minimum duration of 2 years. Conclusion: Intervention in the early stages can avoid radical procedures such as wide local excision or amputation. We recommend aggressive surgical approach with close follow-up to detect recurrence if any, at an early stage.

10.
J Orthop Case Rep ; 13(10): 115-120, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37885646

ABSTRACT

Introduction: Cervical Pott's constitutes about 10% of all Pott's spine cases. In tuberculous spondylitis, initially there occurs destruction of vertebral bodies and further progression may result in adjacent abscesses, leading to cord compression. Objective is to excise the diseased focus and to provide spinal stability. Case Report: We are presenting 3 rare cases of cervical Pott's spine with epidural collection at multiple levels in the cervical region without significant vertebral body destruction that were followed up for a period of 1 year postoperatively. Patients underwent single-level corpectomy and decompression from anterior aspect. In all three cases, we were able to decompress the cord and remove all the collections and also achieved spinal stabilization. Patients had a gradual and complete recovery of motor power within 6 months to 1 year after surgery. Conclusion: Technique used allows accurate visual assessment of the extent of the disease and allows complete decompression of the cord at multiple levels in cervical spine without causing much instability.

11.
J Orthop Case Rep ; 13(10): 24-27, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37885656

ABSTRACT

Introduction: As the number of patients undergoing spine fixation has increased, the requirement for revision surgery has also increased. Difficulty faced while doing revision surgery is mostly in removing polyaxial pedicle screws, especially if we do not have the desired instrumentation. Case Report: A 55-year-old patient previously operated for D12 fracture presented to us with implant failure due to backing out of pedicle screws. Compatible instrumentation to remove the implant was not available as even the cap screw could not be removed due to screwdriver mismatch. Hence, we had to design our own method to address the problem which we did successfully. At present, the patient is on our regular follow-up, is pain free, is able to walk without support, and has not reported any new complaints. Conclusion: Method used in our case simplifies and accelerates the screw removal process and provides guidance to any surgeon who faces a similar problem.

12.
J Orthop Case Rep ; 13(9): 10-13, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37753127

ABSTRACT

Introduction: Osteochondroma is the most common benign tumor of bone. Tumors are metaphyseal in origin and commonly involve distal femur, proximal tibia, and proximal fibula in the lower extremity. Osteochondroma located at proximal fibula can change the normal path of nerves and it may lead to the compression of vessels or peroneal nerve, leading to paralysis. Case Report: We are reporting a case of an 18-year-old female with proximal fibular osteochondroma causing splitting of common peroneal nerve without any neuropathy. Conclusion: We strive to make the surgeons aware that, when removing osteochondroma located at proximal fibula, care should be taken to identify the entire nerve at the site of lesion before the removal as a procedure done in a hurry in such a case can cause irreversible damage to the patient.

14.
Transpl Immunol ; 80: 101898, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37437666

ABSTRACT

BACKGROUND: Neutrophil extracellular traps (NETs) have a role in infection, autoimmunity, autoinflammation, thrombosis, ischemia-reperfusion injury (IRI), epithelial-mesenchymal transition, vasculitis, and metabolic diseases. However, its role in early graft injury and graft outcome has not been elucidated till now. We evaluated the circulating NETs during early post-transplant periods and their correlation with graft outcome and IRI. METHODS: Prospectively, thirty kidney transplants recipient (KTR) were recruited and grouped into non-dysfunction (Group-A) and dysfunction groups (Group-B). Serum levels of circulating NETs were estimated by measuring myeloperoxidase-DNA complex at three-time points: pre-transplant, 8 h post-transplant, and 18 h post-transplant; and correlated with early graft outcome. Malondialdehyde (MDA), a marker of oxidative stress or IRI, was also measured to assess its relation with NETs and early graft outcome. RESULTS: Circulating NETs were significantly increased in both non-dysfunctional [Median OD: 0.11 (0.01-0.19) to 0.51 (0.22-0.91); p = 0.001] and dysfunctional [Median OD: 0.16 (0.12-0.27) to 0.38 (0.19-0.68); p = 0.047] KTR during first 8 h of transplant followed by fall at 18 h post-transplant [0.25 (0.18-0.72) and 0.35 (0.26-0.36) respectively]; however, no significant difference were observed between two groups at any time points. Isolated biopsy-proven graft rejection KTR also had higher circulating NETs during the early post-transplant period [Median OD: 0.16 (0.13-0.31) to 0.38 (0.28-1.5); p > 0.05] but no significant difference compared to non-dysfunctional KTR. MDA also displayed similar trends with an early significant rise [9.30 (7.74-12.56) µM to 17.37 (9.11-22.25) µM; p = 0.03 in group-A, and 8.7 (6.04-10.30) µM to 14.66 (13.39-21.63) µM; p = 0.01in group-B] followed by fall at 18 h in both groups [10.21 (7.64-13.90) µM and 11.11 (9.15-17.54) µM respectively]. Despite similar trends of both NETs and MDA, there was no significant correlation between these; however, creatinine exhibits a significant inverse correlation with NETs and MDA both. CONCLUSION: Circulating NETs are significantly increased during the early post-transplant period in KTR irrespective of early graft outcome. Similar dynamics of MDA indicate that the early rise of NETs might be a part of IRI. However, molecular studies with large sample sizes and longer follow up are required to reach more defined conclusions.

15.
J Cancer Res Ther ; 19(Supplement): S12-S19, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37147978

ABSTRACT

Treatment of multiple myeloma has undergone significant advances in the last two decades, leading to meaningful improvement in overall and progression free survival. The incurable nature of disease necessitates serial sequencing of treatment options and continuous therapy once disease remission is achieved. Autologous stem cell transplantation (ASCT) has continued to offer a meaningful survival advantage with a consistent reduction in toxicity and costs. Despite the advent of newer drugs leading to deeper and sustained responses, ASCT continues to be the standard of care for all eligible patients and is ostensibly more cost effective than continued treatment with newer agents. However, ASCT continues to be underutilized in India, due to concerns about cost, safety, and sporadic expertize. We present a systematic review of available data on ASCT for multiple myeloma from India to evaluate safety and efficacy of the procedure, and provide evidence re-affirming its utility in resource constrained settings.


Subject(s)
Hematopoietic Stem Cell Transplantation , Multiple Myeloma , Humans , Multiple Myeloma/drug therapy , Transplantation, Autologous , Progression-Free Survival , India
17.
Clin Lymphoma Myeloma Leuk ; 23(5): 360-369.e1, 2023 05.
Article in English | MEDLINE | ID: mdl-36849307

ABSTRACT

INTRODUCTION: We report one of the largest single center data from a mixed referral setting in India describing baseline characteristics and outcomes of patients with classical BCR::ABL1 negative myeloproliferative neoplasms (MPNs). MATERIALS AND METHODS: Patients diagnosed from June 2019 to 2022 were included. Workup and treatment was as per current guidelines. RESULTS: Diagnosis comprised polycythemia vera (PV) in 51(49%), ET in 33(31.7%) and prefibrotic primary myelofibrosis (MF) pre fibrotic myelofibrosis (prePMF) and myelofibrosis in 10(9.6%) patients each. Median age at diagnosis was 52 years for PV and ET, 65.5 for MF and 79 years for prePMF. Diagnosis was incidental in 63(56.7%) and after thrombosis in 8(7.2%) patients. Baseline next generation sequencing (NGS) was available for 63(60.5%) patients. Driver mutations in PV: JAK2 in 80.3%; in ET: JAK2 in 41%, CALR in 26%, MPL in 2.9%; in prePMF JAK2 in 70%, CALR in 20%, MPL in 10%, and in MF: JAK2 in 10%, MPL in 30% and CALR in 40%. Seven novel mutations were detected of which 5 were potentially pathogenic on computational analysis. After median follow up of 30 months, 2 patients had disease transformation and none had new episodes of thrombosis. Ten patients died, most commonly with cardiovascular events(n = 5,50%). Median overall survival was not reached. Mean OS time was 10.19 years(95%CI, 8.6 to 11.74) and mean time to transformation was 12.2 years(95% CI,11.8 to 12.6). CONCLUSION: Our data indicates comparatively indolent presentation of MPNs in India with younger age and lower risk of thrombosis. Further follow up will enable correlation with molecular data and guide modification of age based risk stratification models.


Subject(s)
Myeloproliferative Disorders , Polycythemia Vera , Primary Myelofibrosis , Humans , Calreticulin/genetics , Janus Kinase 2/genetics , Mutation , Myeloproliferative Disorders/diagnosis , Myeloproliferative Disorders/genetics , Polycythemia Vera/diagnosis , Primary Myelofibrosis/diagnosis , Primary Myelofibrosis/genetics , Primary Myelofibrosis/pathology , Receptors, Thrombopoietin/genetics
18.
Clin Exp Med ; 23(5): 1801-1813, 2023 Sep.
Article in English | MEDLINE | ID: mdl-36219364

ABSTRACT

ANCA-associated vasculitis (AAV) is a life-threatening disease characterized by small vessel inflammation and pathogenic self-directed antibodies. Programmed death-ligand 1 receptor (PD-1) and programmed cell death ligand-1 (PD-L1) are immune checkpoint molecules crucial for maintaining tolerance and immune homeostasis. After checkpoint inhibition therapy, development of various autoimmune diseases and immune-related adverse events (irAEs) have been observed. Here, we investigated the immunomodulatory roles of neutrophils through the expression of immune checkpoint molecule (PD-L1), migratory molecules (CXCR2), chemotactic chemokines (CXCL5) and other important molecules (BAFF and HMGB1) in development of AAV. We also scrutinized the immune mechanism responsible for development of pauci-immune crescentic GN (PICGN). We demonstrate for the first time that the frequency of PD-L1 expressing neutrophils was significantly reduced in AAV patients compared to healthy controls and correlated negatively with disease severity (BVASv3). Further, in renal biopsy, reduced PD-L1 immune checkpoint expression provides a microenvironment that unleashes uncontrolled activated CD4 + T cells, B cells, neutrophils and macrophages and ultimately causes engulfment of immune complexes leading to PICGN. Furthermore, during remission, reduced neutrophils PD-L1 and CXCR2 expression, increased neutrophils CXCL5 expression and increased peripheral effector memory T cells and increased HMGB1 and BAFF levels in serum, demonstrate the propensity for the persistence of sub-clinical inflammation, which could explain relapse, in this group of diseases.


Subject(s)
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis , HMGB1 Protein , Humans , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , B7-H1 Antigen/metabolism , Chemokines , Inflammation/complications , T-Lymphocyte Subsets
19.
Clin Exp Med ; 23(3): 917-927, 2023 Jul.
Article in English | MEDLINE | ID: mdl-35881260

ABSTRACT

Chronic nasal carriage of Staphylococcus aureus (S. aureus) is a risk factor for relapse of granulomatosis with polyangiitis (GPA), and genetic susceptibility to infections and autoimmune diseases is majorly affected by HLA genes. Previous studies have shown the association of HLA Class-II genes with GPA susceptibility. Here, we aim to assess immune responses of GPA patients against S. aureus antigens in relation to the HLA-DR-DQ genes polymorphism to determine the disease outcome. A total of 45 GPA patients and 128 healthy controls during 2010-2012 were included in this case-control study. HLA-DRB1/DQB1 allele typing was performed by polymerase chain reaction-sequence-specific primer (PCR-SSP) method. Immune responses against S. aureus antigens were investigated in 20 active vs. remitting GPA (after 6 months of cyclophosphamide and glucocorticoids) patients by Western blot. Statistical analysis was performed using χ2 test and Fisher's exact test. We observed a significant association of DRB1*08, DRB1*16 and DQB1*04 alleles with GPA susceptibility, whereas DRB1*15, DRB1*10 and DQB1*05 alleles were suggested as protective alleles. Among S. aureus antigens, active GPA patients' sera reacted more strongly with 34 and 24 kDa antigens of S. aureus than remitting and healthy control  sera. Furthermore, we observed that the lack of DQB1*06 allele confers complete remission even in the presence of anti-S. aureus antibodies against 24 kDa protein. Our findings suggest that the presence of DQB1*06 allele and S. aureus infection may prolong active disease. Further, our study indicates the potential of using anti-staphylococcal medications for achieving remission in patients having HLA-DQB1*06 allele.


Subject(s)
Granulomatosis with Polyangiitis , HLA-DQ Antigens , Humans , Gene Frequency , HLA-DQ Antigens/genetics , Case-Control Studies , Granulomatosis with Polyangiitis/drug therapy , Granulomatosis with Polyangiitis/genetics , HLA-DRB1 Chains/genetics , Alleles , Genetic Predisposition to Disease , Haplotypes
20.
Int J Mycobacteriol ; 11(4): 384-388, 2022.
Article in English | MEDLINE | ID: mdl-36510922

ABSTRACT

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.


Subject(s)
Crohn Disease , Tuberculosis, Gastrointestinal , Humans , Crohn Disease/diagnosis , Cross-Sectional Studies , Cytokines , Interleukin-10 , Interleukin-17/therapeutic use , Transforming Growth Factor beta/therapeutic use , Transforming Growth Factors/therapeutic use , Tuberculosis, Gastrointestinal/diagnosis , Tuberculosis, Gastrointestinal/drug therapy
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