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Background Cytomegalovirus (CMV) reactivation or infection is one of the most important infectious complications in transplant recipient leading to significant morbidity and mortality. Its early detection and prompt treatment is imperative to improve transplant outcome. The present study estimated the frequency of CMV in renal transplant recipients (RTR). Various aspects of pp65Ag assay and quantitative real-time polymerase chain reaction (qRT-PCR) were evaluated in relation to the recent guidelines for CMV detection and treatment. Methods Retrospectively, data of clinically suspected cases of CMV (1610 out of total 2681 renal transplants) were analyzed along with a comparison of pp65Ag assay and qRT-PCR. Results The overall incidence of CMV syndrome was 14.25%; however, the incidence of CMV viremia in the clinically suspected group was 23.73%. The proportion of positive cases with pp65Ag assay and qRT-PCR were 13.6% (95% CI; 7.9-22.3) and 19.3% (95% CI; 12.4-28.8) with a substantial agreement (Cohen’s kappa = 0.632) between the 2 techniques. CMV positive recipients were treated with ganciclovir until their viral count was negative or up to 3 weeks, followed by 3 months of prophylaxis with valganciclovir. No graft failure or mortality was reported secondary to CMV infection until 3 to 5 years of follow-up. Results CMV infection is quite prevalent in RTR, and early detection and immediate treatment or prophylaxis is of utmost importance. qRT-PCR is the gold standard and preferred over other methods; however pp65Ag assay still holds its importance in low-economic countries and populations where CMV infection is more prevalent and financial constraints are a major limitation.

To study the expression of B cell-activating factor of tumor necrosis factor family (BAFF) and A proliferation-inducing ligand (APRIL) genes in active and remitting patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) and healthy controls and their correlation with disease activity.This was a prospective case-control study. Gene expressions of BAFF and APRIL were studied in 32 patients with AAV (16 each with active disease and in remission) and 30 healthy age and sex matched controls by real-time polymerase chain reaction.Out of 32 AAV patients, 26 had granulomatosis with polyangiitis (GPA) and 6 had microscopic polyangiitis (MPA). Mean ages of patients in active (12 GPA and 4 MPA) and remission (14 GPA and 2 MPA) groups were 39.4 ± 17.2 and 44.6 ± 16.1 years, respectively. BAFF gene expression was significantly higher in both the active AAV group and remission AAV group compared to controls (P .01). The BAFF expression was significantly higher in AAV patients in remission compared to active AAV patients (P = .003). In contrast, APRIL expression did not differ between AAV patients and controls (P = .829). However, APRIL had significantly higher expression in remission as compared to active patients (P = .048). There was no significant correlation of both BAFF and APRIL expression with disease activity markers (erythrocyte sedimentation rate, C-reactive protein, platelets and Birmingham Vasculitis Activity Score version 3).BAFF gene is significantly expressed in patients with AAV. Among AAV patients, there is a significantly higher expression of BAFF and APRIL in remitting state of the disease as compared to active state. There is no significant change in APRIL gene expression in patients with AAV as compared to controls. This makes a case for anti-BAFF therapy in future for AAV patients in northern India.

Objectives ANCA-associated vasculitis (AAV) can affect all age groups. We aimed to show that differences in disease presentation and 6 month outcome between younger- and older-onset patients are still incompletely understood. Methods We included patients enrolled in the Diagnostic and Classification Criteria for Primary Systemic Vasculitis (DCVAS) study between October 2010 and January 2017 with a diagnosis of AAV. We divided the population according to age at diagnosis: Results A total of 1338 patients with AAV were included: 66% had disease onset at Conclusion Within 6 months of diagnosis of AAV, patients >65 years of age display a different pattern of organ involvement and an increased risk of significant damage and mortality compared with younger patients.

Rituximab is currently used after the conventional agents have failed in the management of steroid-dependent (SD)/ steroid-resistant (SR) podocytopathies and have a safer toxicity profile. We report 53 adults with podocytopathies who were managed effectively with CD19-targeted rituximab therapy. METHODS This was a prospective study carried out at a tertiary care centre in India between January 2014 and June 2019. Adults between 16 and 60 years with SD, frequently relapsing (FR), and SR nephrotic syndrome (NS) due to podocytopathy received rituximab in a CD19-targeted approach. PRIMARY OUTCOME Percentage of patients who were in remission at 6 and 12 months. Secondary outcome: Percentage of patients in remission at the last follow-up, rituximab dose and adverse events of rituximab therapy. RESULTS Fifty-three adults with SD/FR/SR NS received CD19-targeted rituximab. The median age at the time of first rituximab injection was 30.09 ± 13.21 (16.53) years. At the time of first rituximab infusion, all patients were in remission with steroids and/or calcineurin inhibitors (CNIs). Fifty (94.33%) patients were in remission at the end of 6 and 12 months and the last follow-up (median: 36 months). The mean total dose of rituximab at 1 year was 788.7 ± 128.1 (6 001 100) mg. At last follow-up (median 36 months), 42 (79%) patients did not require any additional CNI or steroids therapy. No serious adverse events to rituximab were noted. CONCLUSION CD19-targeted rituximab therapy is safe and efficacious in the management of SD/SR adult podocytopathy. Also, rituximab is effective in maintaining remission in treatment naive adult SD or FR podocytopathy.

AIM Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is an autoimmune disease characterized by necrotizing small vessel vasculitis that can affect various organs and present multiple symptoms. Susceptibility to AAV is multifactorial and most likely caused by an amalgamation of genetic and environmental factors. The aim of the present study was to explore the distribution of human leukocyte antigen (HLA)-DRB1/DQB1, protein tyrosine phosphatase non-receptor type 22 (PTPN22) and cytotoxic T-Lymphocyte-associated protein 4 (CTLA-4) polymorphisms in North Indian AAV patients and their associations with clinical and pathological characteristics associated with the disease. METHODS A total of 150 AAV patients and 150 healthy controls were recruited. The clinical classification showed 128 as granulomatosis with polyangiitis (GPA) and 21 as microscopic polyangiitis. Only 1 case of eosinophilic granulomatosis with polyangiitis was encountered, which was excluded from analysis. HLA-DRB1/DQB1 alleles were determined by polymerase chain reaction-sequence-specific primer (PCR-SSP) method and single nucleotide variant genotyping for CTLA-4 and PTPN22 was done by simple probe-based SNP arrays. RESULTS A significant predispositional association of DRB1*03 and DQB1*02 alleles, were confirmed in proteinase 3 (PR3)-AAV patients, whereas DRB1*10, DRB1*14 and DQB1*05 were protective alleles in AAV, PR3-AAV and GPA patients. GG genotype of CTLA-4 + 49A/G was increased in patients as compared to controls and showed an association with AAV, PR3-AAV and GPA patients. CONCLUSION The study indicated strong genetic associations were linked with PR3 antineutrophil cytoplasmic antibody specificity and it appears that PR3-AAV and MPO-AAV have distinct genetic backgrounds.

This study aimed to evaluate an association between Epstein-Barr virus (EBV) and systemic sclerosis (SSc).One hundred and fifty (138 female, 12 male) consecutive adult SSc patients fulfilling the American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) criteria were included in this cross-sectional study. Serological analysis by line blot for class immunoglobulin G (IgG) and IgM antibodies against EBV antigen (EBV capsid antigen [VCA] gp125, VCA p19, EBNA-1, p22, EA-D) and quantification of EBV DNA in whole blood by real-time polymerase chain reaction was performed.Class IgM antibodies against VCA gp125 (22.8% vs 0%, P .0002), VCA p19 (55.7% vs 4.4%, P .0001), EBNA1 (35.7% vs 0%, P .0001), p22 (24.2% vs 0%, P .0001), EA-D (14.2% vs 2.2%, P .04), and class IgG antibodies against p22 (95.7% vs 82.2%, P .02) and EA-D (54.2% vs 0%, P .0001) reactivities were significantly higher in SSc patients than in controls. The past infection was significantly associated with the control group (42.8% vs 91%, P .0001); and the viral reactivation was significantly associated with the SSc group (55.7% vs 4.4%, P .0001). Only three (2%) out of 150 SSc patients were positive for EBV DNA, similar to the control group (2%) (P .9).The study shows a strong serological association of EBV (reactivation stage) with SSc patients in the absence of viral DNA in the circulation, indicating the EBV reservoir or tropism presence elsewhere.

IntroductionThe WHO recommends community mobilisation with women’s groups practising participatory learning and action (PLA) to improve neonatal survival in high-mortality settings. This intervention has not been evaluated at scale with government frontline workers.MethodsWe did a pragmatic cluster non-randomised controlled trial of women’s groups practising PLA scaled up by government front-line workers in Jharkhand, eastern India. Groups prioritised maternal and newborn health problems, identified strategies to address them, implemented the strategies and evaluated progress. Intervention coverage and quality were tracked state-wide. Births and deaths to women of reproductive age were monitored in six of Jharkhand’s 24 districts: three purposively allocated to an early intervention start (2017) and three to a delayed start (2019). We monitored vital events prospectively in 100 purposively selected units of 10 000 population each, during baseline (1 March 2017–31 August 2017) and evaluation periods (1 September 2017–31 August 2019). The primary outcome was neonatal mortality.ResultsWe identified 51 949 deliveries and conducted interviews for 48 589 (93.5%). At baseline, neonatal mortality rates (NMR) were 36.9 per 1000 livebirths in the early arm and 39.2 in the delayed arm. Over 24 months of intervention, the NMR was 29.1 in the early arm and 39.2 in the delayed arm, corresponding to a 24% reduction in neonatal mortality (adjusted OR (AOR) 0.76, 95% CI 0.59 to 0.98), including 26% among the most deprived (AOR 0.74, 95% CI 0.57 to 0.95). Twenty of Jharkhand’s 24 districts achieved adequate meeting coverage and quality. In these 20 districts, the intervention saved an estimated 11 803 newborn lives (min: 1026–max: 20 527) over 42 months, and cost 41 international dollars per life year saved.ConclusionParticipatory women’s groups scaled up by the Indian public health system reduced neonatal mortality equitably in a largely rural state and were highly cost-effective, warranting scale-up in other high-mortality rural settings.Trial registrationISRCTN99422435.

Aim: A significant proportion of patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are either steroid dependent (SD) or resistant (SR), requiring long-term calcineurin inhibitors (CNIs) use. Rituximab has more favourable safety profile. The present study was undertaken to evaluate the efficacy and safety of rituximab in CNI dependent patients.Methods: This was a prospective observational study conducted from July 2014 to February 2018. SD-NS or SR-NS (biopsy proven MCD/FSGS), who were CNI dependent were enrolled. Mean age at enrolment was 22.77±7.45 years. All patients received rituximab at a dose of 375 mg/m2 at entry in the study. CD-19 levels were monitored monthly and patients having CD-19 levels >5/μL and/or >1% received additional low-dose (100 mg) of rituximab.Results: A total of 24 patients were followed up for 12 months. At the end of 6 and 12 months, 87.5 and 79.16% of the patients achieved remission, respectively. Eight (33.33%) patients developed relapse. The mean dose of rituximab in the first year was 791 mg. The average cost of rituximab in the first year was 487.17$. Rituximab was well- tolerated, with mild infusion reactions, respiratory tract infection and oral candidiasis in 5 (20.83%), 5 (20.83%) and 1 (4.17%) patient, respectively.Conclusions: CD-19 targeted rituximab is a safe and cost-effective agent in remission maintenance in adults with CNI dependent. Over three-fourths of the patients with CNI dependent podocytopathy maintain clinical remission with CD-19 targeted rituximab therapy

IntroductionIn a large developing country, with diverse population characteristics and differential access to healthcare, it is important to identify factors that influence postnatal health. This knowledge will help frame recommendations to enhance universal postnatal care.Methods and analysisA prospective cohort study will be conducted by recruiting all participants who deliver in a referral centre in South India during a 1-year period after written consent is obtained from them. In addition to clinical information pertaining to their delivery and demographics, details of physical health, mental health socioeconomic status and emotional support will also be collected. Every participant will be followed up physically and/or by telephonic consultation at 3, 9 and 18 months of their postnatal period to reassess their status and that of their babies. As there are several independent and dependent variables requiring multivariate analysis, a sample size of 10 000 is considered adequate. Any unplanned visits to a health facility will be enquired into and documented for analysis.During data analysis, the effect of Caesarean section, high-risk characteristics and gestational age of the baby at delivery on various outcome measures and postnatal status will be evaluated. Interpretation of the large volume of collected data will help frame recommendations to improve postnatal careEthics and disseminationThe study is approved by the Institutional Review Boards (Research and Ethics Committees) of Christian Medical College, Vellore, Tamil Nadu, India (IRB 12178 date 24 June 2020).Women are provided with a detailed information sheet and written consent is obtained. They are reassured that their care will not be compromised if they do not consent to the study. Data will be available on the clinical trial portal to assist in the dissemination of results after the project is published.Trial registration numberCTRI/2022/03/041343.

The objectives of this study were to describe the clinical features and evaluate the utility of immunological features as predictors of organ involvement and disease severity in patients with primary Sjogren's syndrome (pSS). In this single-center observational cross-sectional study, subjects fulfilling the 2012 AECG criteria or 2016 ACR/EULAR criteria for pSS were included. Details of glandular, extra-glandular manifestations, ESSDAI, ESSPRI, ANA, anti-Ro/La antibodies, rheumatoid factor (RF), complement (C3 and C4) levels and hyperglobulinemia were noted. Chi-square and Mann-Whitney U tests were performed for determining associations and relative risk (RR) was calculated. Sixty-four subjects with pSS were included in the study. Females constituted 92% and median age at onset was 37.5 (15-74) years. Ocular or oral sicca was noted in 61 (95.3%) subjects and parotidomegaly was noted in 17 (26.5%) subjects. Extra-glandular manifestations noted were: constitutional (85.9%), articular (65.6%), renal (29.6%), hematological (26.6%), cutaneous (12.5%), peripheral nerves (9.3%) and pulmonary (4.7%). Immunological features noted were: ANA (85.9%), anti-Ro (81.3%), anti-La (60.9%), RF (84.4%), hypocomplementemia (39.1%) and hyperglobulinemia (62.5%). Median ESSDAI was 6 (0-23) and ESSPRI was 7 (0-10). ANA was associated with younger age and renal involvement (RR 1.25). Anti-Ro was associated with younger age, renal involvement (RR 1.36) and high ESSDAI. Anti-La was associated with high renal (RR 3.4) and low articular involvement (RR 2.75). RF was associated with hematological involvement and hyperglobulinemia was associated with younger age. Certain immunological features can help predict the organ involvement in patients with pSS. Larger, prospective follow-up studies are needed to clearly understand these associations.

The 1990 American College of Rheumatology (ACR) criteria for the classification of polyarteritis nodosa (PAN) have many pitfalls and performed poorly when used for diagnostic purposes. Recently, a provisional seven-item diagnostic criteria for PAN was proposed. To validate the provisional seven-item diagnostic criteria for PAN in a cohort of PAN patients from a tertiary care centre in India. Clinical details of patients diagnosed as PAN as per the European Medicines Agency algorithm between 2005 and 2020 were collected retrospectively. Age and sex-matched anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) patients were included in the non-PAN group. Patients with a deficiency of adenosine deaminase 2 (DADA2) were included as a separate group. The sensitivity, specificity, positive and negative predictive values (PPV and NPV) for ACR criteria, the Ministry of Health, Labour and Welfare (MHLW) in Japan diagnostic criteria and the seven-item diagnostic criteria were calculated. Thirty-seven PAN, 14 DADA2 and 37 AAV patients were included in the analysis. The sensitivity, specificity, PPV and NPV of the seven-item criteria were 83.7%, 96.8%, 97.3% and 81.1% respectively. For the ACR criteria, sensitivity was 82.9% and specificity was 79.5%. The sensitivity, specificity for MHLW criteria were 77.3% and 90% respectively. The sensitivity and specificity of seven-item criteria for DADA2 patients were 58.8% and 88.2% respectively. There was very poor agreement between the ACR criteria and the seven-item and MHLW criteria and fair agreement between seven-item and MHLW criteria (κ = 0.279). The provisional seven-item criteria for PAN performed well with high specificity and PPV.

BackgroundSevere Combined Immune Deficiency (SCID) is an inherited defect in lymphocyte development and function that results in life-threatening opportunistic infections in early infancy. Data on SCID from developing countries are scarce.ObjectiveTo describe clinical and laboratory features of SCID diagnosed at immunology centers across India.MethodsA detailed case proforma in an Excel format was prepared by one of the authors (PV) and was sent to centers in India that care for patients with primary immunodeficiency diseases. We collated clinical, laboratory, and molecular details of patients with clinical profile suggestive of SCID and their outcomes. Twelve (12) centers provided necessary details which were then compiled and analyzed. Diagnosis of SCID/combined immune deficiency (CID) was based on 2018 European Society for Immunodeficiencies working definition for SCID.ResultsWe obtained data on 277 children; 254 were categorized as SCID and 23 as CID. Male-female ratio was 196:81. Median (inter-quartile range) age of onset of clinical symptoms and diagnosis was 2.5 months (1, 5) and 5 months (3.5, 8), respectively. Molecular diagnosis was obtained in 162 patients - IL2RG (36), RAG1 (26), ADA (19), RAG2 (17), JAK3 (15), DCLRE1C (13), IL7RA (9), PNP (3), RFXAP (3), CIITA (2), RFXANK (2), NHEJ1 (2), CD3E (2), CD3D (2), RFX5 (2), ZAP70 (2), STK4 (1), CORO1A (1), STIM1 (1), PRKDC (1), AK2 (1), DOCK2 (1), and SP100 (1). Only 23 children (8.3%) received hematopoietic stem cell transplantation (HSCT). Of these, 11 are doing well post-HSCT. Mortality was recorded in 210 children (75.8%).ConclusionWe document an exponential rise in number of cases diagnosed to have SCID over the last 10 years, probably as a result of increasing awareness and improvement in diagnostic facilities at various centers in India. We suspect that these numbers are just the tip of the iceberg. Majority of patients with SCID in India are probably not being recognized and diagnosed at present. Newborn screening for SCID is the need of the hour. Easy access to pediatric HSCT services would ensure that these patients are offered HSCT at an early age.

BackgroundThere is paucity of literature on XLA from developing countries. Herein we report the clinical and molecular profile and outcome in a multicenter cohort of patients with XLA from India.MethodsData on XLA from all regional centers supported by the Foundation for Primary Immunodeficiency Diseases (FPID), USA and other institutions providing care to patients with PIDs were collated. Diagnosis of XLA was based on European Society for Immunodeficiencies (ESID) criteria.ResultsWe received clinical details of 195 patients with a provisional diagnosis of XLA from 12 centers. At final analysis, 145 patients were included (137 ‘definite XLA’ and eight ‘probable/possible XLA’). Median age at onset of symptoms was 12.0 (6.0, 36.0) months and median age at diagnosis was 60.0 (31.5, 108) months. Pneumonia was the commonest clinical manifestation (82.6%) followed by otitis media (50%) and diarrhea (42%). Arthritis was seen in 26% patients while 23% patients developed meningitis. Bronchiectasis was seen in 10% and encephalitis (likely viral) in 4.8% patients. Pseudomonas aeruginosa was the commonest bacterial pathogen identified followed by Streptococcus pneumoniae, Staphylococcus aureus and Klebsiella pneumoniae. Molecular analysis revealed 86 variants in 105 unrelated cases. Missense variants in BTK gene were the most common (36%) followed by frameshift (22%) and nonsense variants (21%). Most pathogenic gene variants (53%) were clustered in the distal part of gene encompassing exons 14–19 encoding for the tyrosine kinase domain. Follow-up details were available for 108 patients. Of these, 12% had died till the time of this analysis. The 5-year and 10-year survival was 89.9% and 86.9% respectively. Median duration of follow-up was 61 months and total duration of follow-up was 6083.2 patient-months. All patients received intravenous immunoglobulin (IVIg) replacement therapy. However, in many patients IVIg could not be given at recommended doses or intervals due to difficulties in accessing this therapy because of financial reasons and lack of universal health insurance in India. Hematopoietic stem cell transplant was carried out in four (2.8%) patients.ConclusionThere was a significant delay in the diagnosis and facilities for molecular diagnosis were not available at many centers. Optimal immunoglobulin replacement is still a challenge

Deficiency of adenosine deaminase 2 (DADA2) is a potentially fatal monogenic syndrome characterized by variable manifestations of systemic vasculitis, bone marrow failure, and immunodeficiency. Most cases are diagnosed by pediatric care providers, given the typical early age of disease onset. This study was undertaken to describe the clinical phenotypes and treatment response both in adults and in children with DADA2 in India.A retrospective analysis of pediatric and adult patients with DADA2 diagnosed at various rheumatology centers across India was conducted. Clinical characteristics, diagnostic findings, and treatment responses were analyzed in all subjects.In total, 33 cases of DADA2 were confirmed in this cohort between April 2017 and March 2020. Unlike previous studies, nearly one-half of the confirmed cases presented during adulthood. All symptomatic patients exhibited features of vasculitis, whereas constitutional symptoms and anemia were more common in pediatric patients. Cutaneous and neurologic involvement were common, and 18 subjects had experienced at least one stroke. In addition, the clinical spectrum of DADA2 was expanded by recognition of novel features in these patients, including pancreatic infarction, focal myocarditis, and diffuse alveolar hemorrhage. Treatment with tumor necrosis factor inhibitors (TNFi) was initiated in 25 patients. All of the identified disease manifestations showed marked improvement after initiation of TNFi, and disease remission was achieved in 19 patients. Two cases were complicated by tuberculosis infection, and 2 deaths were reported.This report presents the first case series of patients with DADA2 from India, diagnosed by adult and pediatric care providers. The findings raise awareness of this syndrome, particularly with regard to its presentation in adults.

Introduction:Hyper-IgE Syndrome (HIES) is a rare inborn error of immunity (IEI) characterized by a constellation of symptoms related to susceptibility toStaphylococcalskin and pulmonary infections, eczema, raised serum IgE (>2,000 IU/ml), craniofacial anomalies, and recurrent bone fractures. Data on HIES from the Indian subcontinent is scarce and restricted to small case series and case reports. This is the first compilation of national data on HIES.Materials and Methods:A total 103 cases clinically diagnosed and treated as HIES were analyzed from nine centers. Cases with clinical and/or molecular diagnosis of DOCK8 deficiency were not included. Patients were divided into two groups: group I for whom a heterozygous rare variant of STAT3 was identified, and group II, with clinical features similar to those of AD STAT3 deficiency, but without any genetic diagnosis.Results:Genetic diagnosis was available in 27 patients (26.2%) and all harbored rare variants in the STAT3 gene. Majority of these STAT3 HIES patients presented with recurrent skin abscesses (77.7%) or pneumonia (62.9%) or both (59.2%). Other features included eczema (37%), candidiasis (55.5%), facial dysmorphism (55.5%), recurrent fractures (11.1%), and retained primary teeth (7.4%).Mycobacterialinfections were seen in a significant 18.5%. Mortality was seen in three subjects (11.1%). A similar trend in the clinical presentation was observed when all the 103 patients were analyzed together. Twenty percent of patients without a rare variant in the STAT3 gene had an NIH score of ≥40, whereas, 51.9% of STAT3 HIES subjects had scores below the cut off of ≥40. TH17 cell numbers were low in 10/11 (90.9%) STAT3 HIES tested. Rare variants observed were 8 in exon 21; 8 in exon 13; 3 in exon 10; 2 in exon 15, and one each in exon 6, 16, 17, 19, 22, and splice site downstream of exon 12. Seven variants were novel and included F174S, N567D, L404Sfs*8, G419 =, M329K, T714I, R518X, and a splice site variant downstream of exon 12.Conclusions:The report includes seven novel STAT3 variants, including a rare linker domain nonsense variant and a CC domain variant.Mycobacterialdiseases were more frequent, compared to western literature.

Plasmodium falciparum gametocytes, the sexual stage responsible for malaria parasite transmission from humans to mosquitoes, are key targets for malaria elimination. Immature gametocytes develop in the human bone marrow parenchyma, where they accumulate around erythroblastic islands. Notably though, the interactions between gametocytes and this hematopoietic niche have not been investigated. Here, we identify late erythroblasts as a new host cell for P falciparum sexual stages and show that gametocytes can fully develop inside these nucleated cells in vitro and in vivo, leading to infectious mature gametocytes within reticulocytes. Strikingly, we found that infection of erythroblasts by gametocytes and parasite-derived extracellular vesicles delay erythroid differentiation, thereby allowing gametocyte maturation to coincide with the release of their host cell from the bone marrow. Taken together, our findings highlight new mechanisms that are pivotal for the maintenance of immature gametocytes in the bone marrow and provide further insights on how Plasmodium parasites interfere with erythropoiesis and contribute to anemia in malaria patients.

Aim Antineutrophil cytoplasmic antibody-associated vasculitides (AAV) are a group of small vessel vasculitis with systemic presentations and considerable morbidity and mortality. Pregnancy in these patients poses a significant therapeutic challenge. There is limited published literature regarding pregnancy in AAV. Methods Two cases of successful pregnancy outcomes in patients with active AAV are described. A systematic review was conducted on the lines of the PRISMA statement for conducting systemic reviews: PubMed (inception of PubMed until 30 April 2017, English language only) and EmBase databases were searched using the following terms: 'pregnancy' AND 'ANCA associated vasculitis' OR 'granulomatosis with polyangiitis' OR 'eosinophilic granulomatosis with polyangiitis' OR 'microscopic polyangiitis' OR 'Churg-Strauss syndrome' OR 'Wegener's granulomatosis'. Results One hundred and thirty-seven pregnancies were documented in 110 patients of AAV. Vasculitis diagnosis was made before pregnancy in 69, during pregnancy in 32 and after pregnancy in 9 patients. Mean age at the time of pregnancy was 29.3 ± 5.3 years. There were 91 term pregnancies, 28 were preterm pregnancies, 15 abortions and 3 still births; 78 had normal delivery and 26 had caesarian section. Conclusion Successful pregnancies have been reported in AAV patients.

AIM To study the profile of autoantibodies on long-term follow-up of children with Kawasaki disease (KD). PATIENTS AND METHODS In this single-center observational cohort study, 50 children who had been diagnosed and treated for KD with a minimum follow-up period of 3 years were enrolled. The organ-specific autoantibodies that were assessed in the study included anti-thyroid microsomal antibody (TMA), anti-parietal cell antibody (PCA) and anti-liver kidney microsomal (LKM) antibody. The organ-nonspecific autoantibodies that were studied included anti-endothelial cell antibody (AECA), anti-nuclear antibody (ANA), anti-neutrophil cytoplasmic antibody (ANCA), anti-mitochondrial antibody (AMA) and anti-smooth muscle antibody (SMA). RESULTS The sample for assessment of serology was taken at a mean follow-up period of 6.41 years (±1.95 SD) after diagnosis. Autoantibodies were detected in 11/50 (22%) patients. ANA was detected in three patients, TMA was positive in seven and ANCA was positive in one. CONCLUSIONS These autoantibodies likely develop in children with KD during the acute stage and may persist for many years. There is no concrete evidence to suggest that these children are at increased risk of developing an autoimmune disease in the future. However, there is some justification for prolonged surveillance for development of autoimmune manifestations.

Pulmonary vaccination is one of the most promising routes for immunization owing to its noninvasive nature and induction of strong mucosal immunity and systemic response. In the present study, recombinant hepatitis B surface antigen loaded solid fat nanoemulsions (SFNs) as carrier system and monophosphoryl lipid A as an adjuvant-carrier system was prepared and evaluated as multiadjuvanted vaccine system for deep pulmonary vaccination. Deposition and clearance from the deep lung of rats were determined by gamma scintigraphy. Biodistribution of SFNs was determined by the live animal imaging system. SFNs dispersion showed slower clearance as compared with sodium pertechnetate control solution (∗∗∗p

Background Cytomegalovirus (CMV) results in significant morbidity and mortality in Human Immunodeficiency Virus (HIV)-infected individuals. There is paucity of literature on paediatric CMV disease, especially from developing countries. Methods A retrospective review of records of all HIV-infected children with evidence of CMV disease was done. Results A total of 15 children were found to have CMV disease (retinitis in all, pneumonia in two and invasive gastrointestinal disease in one). Median CD4+ T cell count and percentage at diagnosis of CMV disease was 64.5 cells/µl and 3.6%, respectively. Intravenous ganciclovir was used in patients with active CMV disease. Of the 15 children, three died while two were lost to follow-up. Symptomatic patients had poor visual outcome and almost all children who were diagnosed on active screening attained normal vision. Conclusion Retinitis is the most common CMV disease in HIV-infected children. Early detection by active screening and initiation of systemic ganciclovir reduces the morbidity.

Background Antisynthetase syndrome is characterized by a triad of myositis, arthritis, and interstitial lung disease. Anti-Jo-1 is the most common associated autoantibody. This study planned to look at the presentation of anti-Jo-1 antisynthetase syndrome in a single Indian center. Methods and materials This was a medical records review single-center study that included patients with anti-Jo-1 antisynthetase syndrome over 10 years. Results This study included 27 patients with anti-Jo-1 antisynthetase syndrome, with mean age of 40 ± 9.2 years and female preponderance (female-to-male ratio, 4:1). At presentation, the characteristic triad was present in only 4 patients. A majority presented with the incomplete form, with 2 clinical features (of triad) in 11 and single feature (of triad) being present in 12 patients at initial presentation. Seven presented only with polyarthritis, out of which 6 had been earlier diagnosed as rheumatoid arthritis. Time gap from diagnosis of "rheumatoid arthritis" to antisynthetase syndrome ranged from 3 to 20 years. In patients who had only arthritis in the beginning, there was a significantly longer delay to diagnosis of antisynthetase syndrome, higher frequency of rheumatoid factor, and lower frequency of anti-Ro-52. Overall, outcome was good, with Eastern Cooperative Oncology Group class 1 or 2 in most except 2 patients. Conclusions Anti-Jo-1 antisynthetase syndrome commonly presented as incomplete (not a triad) and often only with arthritis. These patients are diagnosed and treated as rheumatoid arthritis for many years, before a diagnosis of antisynthetase syndrome is made. Being aware of this presentation may help in earlier diagnosis by actively searching for subtle clues.

We analyzed the spectrum of biopsy-proven renal disease in a single tertiary care center in North India from 2007 to 2016. A total of 420 biopsies were analyzed. Patients were excluded if clinical details were unavailable or if either the histopathology core or the IF core was inadequate. In the final analysis, 359 biopsies were included. All clinical, laboratory, histopathological, and immunofluorescence (IF) findings were recorded in each case. The usefulness of IF in reaching a definitive diagnosis was also analyzed. The patients were in the age range of 2–94 years; 23.1% were children and 76.9% were adults. Males (60.4%) outnumbered females (39.6%) in all the disease categories except lupus nephritis (LN). Primary glomerular diseases (PGDs) (n = 297, 82.7%) were more common than secondary glomerular diseases (SGDs) (n = 46, 12.8%) and tubulointerstitial diseases (n = 16, 4.5%). The most common PGD was focal segmental glomerulosclerosis (FSGS) (23.4%), followed by minimal change disease (17%) and membranous nephropathy (12.5%), whereas the most common SGD was LN, seen in 9.2%. In the present study, IF helped in reaching the final diagnosis in 44.3%. The entities in which IF was most useful in reaching the final diagnoses were FSGS (31.5%) and IgA nephropathy (14.5%). The final pathological diagnosis correlated with the first clinical possibility in 207 of 359 (57.7%) cases. This 10-year study provides descriptive data and highlights the changing pattern of renal disease possibly due to an increased awareness and referral to higher centers.

Aim To describe the clinical features, treatment and long-term outcomes in north Indian patients with granulomatosis with polyangiitis (GPA). Methods Clinical details, Birmingham Vasculitis Activity Score (BVAS-v3), laboratory data, histopathology findings, treatment details and outcomes of all consecutive patients diagnosed as having GPA between April 2005 and April 2016 were retrieved. European Vasculitis Study Group definitions were used to classify patients into localized, early systemic, generalized, severe and refractory categories. The findings were compared with large single center cohorts from USA, Germany and France. Results One hundred and five patients (median age 40 years; 60 females and 45 males) were diagnosed as having GPA. Median duration of follow up was 28 months. Upper respiratory tract, renal and lung involvement were seen in 76.19%, 51.43% and 67.62% of patients, respectively. Ocular, ear, central nervous system, peripheral nervous system, heart, gastrointestinal and skin involvement were seen in 40.95%, 18.1%, 26.67%, 11.43%, 5.71%, 12.38% and 29.52%, respectively. The median BVAS v3 score was 17. Localized, early systemic, generalized, severe and refractory disease were seen in three, 44, 38, 17 and one patient, respectively. Eighteen patients expired and the cause of death was disease activity in 11, disease activity plus sepsis in four and sepsis alone in three patients. Twenty-six patients experienced relapses. No hemorrhagic cystitis or bladder cancers were observed; however, one patient developed myelodysplastic syndrome during follow up. Conclusion Indian patients are younger and have less arthritis, renal and peripheral nerve involvement as compared to the patients in Western cohorts.

Introduction Psoriasis is a multisystem, immune-mediated inflammatory disease. Some authors have proposed an autoimmune basis for psoriasis; however, till date, it has not been definitely established. This study was conducted to explore the autoimmune nature of psoriasis. Materials and methods This was a prospective study in which 43 psoriasis patients were assessed for detailed clinical, histopathological and immunopathological features to explore the diagnostic utility of subtypes, intensity and number of immunoreactants in lesional and non-lesional skin in these patients. In addition, the sera of these patients were analyzed for the presence of various autoantibodies. Results The patients’ age ranged from 14 to 75 years with a male-to-female ratio of 1.52:1. Nine patients (20.93%) were positive for antinuclear and 2 (4.65%) for antismooth muscle antibodies. Direct immunofluorescence (DIF) was positive in 31 (72%) biopsies from the lesional and 27 (63%) biopsies from non-lesional skin. In all these DIF positive cases, granular deposits of C5b-9 were detected at the dermoepidermal junction. No significant difference was observed on comparing the type and pattern of immunoreactant positivity, among lesional and non-lesional skin biopsies (P > .05). Conclusion No significant association between psoriasis and immunoreactant deposition as well as autoantibody seroprevalence was observed, thereby refuting a definite autoimmune basis for psoriasis.

Aim: This study was designed to enumerate regulatory T-cells (Tregs) and estimate transforming growth factor-β1 (TGF-β1) levels in type 1 diabetic (T1D) patients with respect to disease duration and associated autoimmune diseases. Methods: One hundred and fifty patients and twenty healthy controls were recruited in the study. The patients were subcategorized into eight categories on the basis of disease duration (new onset [NO] and long standing [LS]) and associated diseases, i.e., celiac disease (CD) and autoimmune thyroid disease (AiTD). Treg cells were assessed as CD4+ CD25hi+, FOXP3+ cells and serum TGF-β1 levels were assessed by ELISA. Results: The frequency of Tregs and levels of TGF-β1 were significantly increased in the patients compared to the healthy controls. Among the different categories of the patients, no significant differences were seen for TGF- β1 levels, but for Tregs in patients with T1D and AiTD (P = 0.035). A significant correlation was also found between percentage count of Tregs and TGF-β1 levels in NO cases in all disease subcategories, but not in LS patients. Conclusion: Thus, there was an increased percentage of Tregs and serum levels of TGF-β1 in T1D patients, irrespective of the disease duration and associated autoimmune diseases. The significant correlation in these two parameters at the onset of the disease, but not in LS disease, indicates that the immunological milieu in LS autoimmune diseases is more complicated with disease-associated conditions such as prolonged hyperglycemia, insulin therapy, and/or continued gluten in diet. Treatment and modulation of these long-term complications for improving immunological parameters require further research.

OBJECTIVE The aim of this study was to assess in-hospital (immediate) postoperative pain scores and analgesic consumption (primary goals) and preoperative anxiety and sleep quality (secondary goals) in patients who underwent craniotomy and were treated with pregabalin (PGL). Whenever possible, out-of-hospital pain scores and analgesics usage data were obtained as well. METHODS This prospective, randomized, double-blind and controlled study was conducted in consenting patients who underwent elective craniotomy for brain tumor resection at Tel Aviv Medical Center between 2012 and 2014. Patients received either 150 mg PGL (n = 50) or 500 mg starch (placebo; n = 50) on the evening before surgery, 1.5 hours before surgery, and twice daily for 72 hours following surgery. All patients spent the night before surgery in the hospital, and no other premedication was administered. Opioids and nonsteroidal antiinflammatory drugs were used for pain, which was self-rated by means of a numerical rating scale (score range 0–10). RESULTS Eighty-eight patients completed the study. Data on the American Society of Anesthesiologists class, age, body weight, duration of surgery, and intraoperative drugs were similar for both groups. The pain scores during postoperative Days 0 to 2 were significantly lower in the PGL group than in the placebo group (p < 0.01). Analgesic consumption was also lower in the PGL group, both immediately and 1 month after surgery. There were fewer requests for antiemetics in the PGL group, and the rate of postoperative nausea and vomiting was lower. The preoperative anxiety level and the quality of sleep were significantly better in the PGL group (p < 0.01). There were no PGL-associated major adverse events. CONCLUSIONS Perioperative use of twice-daily 150 mg pregabalin attenuates preoperative anxiety, improves sleep quality, and reduces postoperative pain scores and analgesic usage without increasing the rate of adverse effects. Clinical trial registration no.: NCT01612832 (clinicaltrials.gov)

PurposeIn patients with end-stage renal disease, arteriovenous fistulas (AVFs) are the access of choice for hemodialysis but are often complicated by stenosis. We present single-center experience of 78 ultrasound-guided angioplasty procedures for treating peripheral stenoses of AVFs.MethodsBetween January 2013 and November 2015, 78 angioplasties were performed under ultrasound guidance in 53 patients with end-stage renal disease who were referred from dialysis centers with low flow rate, difficult cannulation, increased cannulation site bleeding, immature or thrombosed AVF. Angioplasties were carried out in the presence of a structural lesion in the AVF resulting in at least 50% reduction in vein diameter with a blood flow of 300 cm/s. Clinical success, anatomical success and post-intervention primary and secondary patency rates at 6, 12, 18 and 24 months were studied.ResultsIn 49/53 patients (92.4%), 74 angioplasty procedures were successfully performed, whereas 4/53 patients (7.6%) had primary failure. A total of 35/49 patients (71.4%) underwent single angioplasty procedure whereas 14/49 patients (28.6%) underwent multiple angioplasty procedures. Post-intervention primary patency rates at 6, 12, 18 and 24 months were 78.6%, 60.2%, 53.8% and 48.9%, respectively. Post-intervention secondary patency rates at 6, 12, 18 and 24 months were 100%, 100%, 95.4% and 89%, respectively. Clinical success and anatomical success was 94.8% and 89.7%, respectively.ConclusionsUltrasound-guided angioplasty is an effective method with good long-term outcomes in selected dialysis patients with peripheral stenosis of AVF.

SummaryBackground Recently, a new population of IL-17-producing CD4 T helper (Th) cells, named Th17, was identified and shown to be involved in various inflammatory and autoimmune diseases, including psoriasis. Aim To determine the frequency of Th17 cells and related cytokines in peripheral blood of patients with psoriasis, and to analyse their association with disease severity. Methods This was a prospective study comprising 34 patients with psoriasis and 24 healthy controls. Clinicoepidemiological details of patients were recorded, and severity of psoriasis was assessed by means of the Psoriasis Area and Severity Index. Circulating Th1 and Th17 cells in untreated patients with psoriasis and healthy controls were quantified by flow cytometry. In sera collected from patients with psoriasis and healthy controls, concentrations of IL-17A and IL-23 were examined by ELISA. Results Increased frequencies of CD4+ IL-17A+ T cells were seen in peripheral blood of patients with psoriasis vulgaris (P < 0.001). Although serum IL-17A and IL-23 concentrations were higher in patients with psoriasis than in controls, the results did not reach statistical significance. We could not find any correlation between the studied T cells or related cytokines and the disease severity. Conclusion Increased serum levels of circulating Th17 cells and related cytokines may contribute to the cutaneous pathology of psoriasis, as well as the inflammatory process that is a hallmark of psoriasis.

Objective To study the prevalence and types of congenital anomalies that present at birth in a secondary-level hospital in South India and its contribution to perinatal mortality. Materials and methods A total of 36,074 births over 10 years, from 2003 to 2013, were studied for the prevalence of gross congenital malformations at birth. It was a descriptive, cross-sectional study using data from the birth register and available medical records. Results The incidence of birth defects was 12.5 per 1000 live births, with musculoskeletal disorders being the commonest, followed by craniovertebral anomalies. The prevalence of anomalies over the past 10 years has not shown any significant change (p= 0.555). Discussion The high prevalence of neural tube defects indicates the need for periconceptional folic acid supplementation and early detection of anomalies, which would help in timely management. Detection of musculoskeletal anomalies would help in counseling patients antenatally.

ELISA for anti-desmoglein antibodies (Dsg) is commonly used for diagnosis and assessment of treatment response in pemphigus vulgaris (PV). The present study was conducted to assess the relationship between salivary and serum Dsg1 and Dsg3 levels, and whether salivary Dsg1 and Dsg3 levels correlate with clinical disease severity of oral mucosal lesions in PV. In total 43, patients with PV with predominantly mucosal involvement were recruited. Both serum and salivary samples were collected from the cases, and salivary samples were also collected from five controls. There was a statistically significant correlation between serum and salivary Dsg1 levels and between serum and salivary Dsg3 levels. There was no correlation between serum or salivary Dsg1 and Dsg3 levels with the objective component of the oral mucosal Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). Serum Dsg1 levels significantly correlated with cutaneous ABSIS, but there was no correlation between cutaneous ABSIS and either salivary Dsg1, salivary Dsg3 or serum Dsg3. As salivary Dsg titres correlate with serum levels, saliva can serve as a simple and noninvasive alternative to serum for Dsg ELISA.

Human Papillomavirus (HPV) is a vital risk-factor for cancer cervix. However, persistent HPV infection results in cervical cancer in only a minority. Probably, HPV subdues the host immune response for persistence, which includes augmentation of HLA-G and plausibly aids in progression to cervical cancer. HLA-G, which comprises of membrane and soluble form, downregulates the host's immune response and generate tolerance. The current study aimed to analyze both forms of HLA-G in fresh tissue and plasma of women with HPV-infected and uninfected cervix and cancer cervix using Western blot and ELISA. The study cohort included 30 women with cervical carcinoma and equal number with normal cervix and 6 with HPV infected cervix. We observed a significant upregulation of membranous HLA-G expression in HPV infected cervix and cervical carcinoma (P 0.001). Interestingly, the pairwise comparison of HLA-G tissue protein expression of the normal cervix and cervical carcinoma, as well as the normal cervix with HPV infected cervix, was significant (P 0.001). Levels of soluble HLA-G were significantly raised in carcinoma cervix. We observed a progressive increase in HLA-G protein expression in HPV infected cervix and cervical carcinoma. These findings compel us to hypothesize that the upregulation of HLA-G expression favors the persistence of HPV in a microenvironment of a submissive host response. This progressive upregulation further leads to cervical cancer. Thus elimination of HPV infection seems to be a desirable proposition to prevent cervical cancer. In the absence of antiviral therapy for HPV, exploration of HLA-G antibody-based therapeutic strategies appear promising.

Background The production of 2 monoclonal proteins characterizes biclonal gammopathic manifestations (BGMs). The available medical literature from India is chiefly restricted to case reports. Objective To study the incidence of BGMs in a tertiary care center in Chandigarh, India, during a 4-year period. We evaluated these cases further for their laboratory characteristics. Methods We scrutinized the contents of a database containing information from the studied 4-year period. Cases reported as BGMs on serum protein electrophoresis (SPEP) and confirmed by serum immunofixation electrophoresis (SIFE) were included. Results A total of 15 cases, from a cohort of 914 cases of monoclonal gammopathic manifestations (MGMs), were available. On SPEP, 2 M bands were observed in 12 cases. On SIFE, 4 cases were reported as being of true BGMs. The most common heavy-chain combination observed was immunoglobulin (Ig)A-IgG. Follow-up was available in 2 patients. Conclusion Identification of BGMs increases diagnostic precision, despite that the treatment is similar to that for monoclonal gammopathic manifestations (MGMs). BGMs can be transitory and may be observed at presentation or during the disease course.

BackgroundMalnutrition among children is one of the most pressing health concerns middle- and low-income countries face today, particularly those in Sub-Saharan Africa and South Asia. Early-life malnutrition has been shown to affect long-term health and income. One hypothesized channel linking early-life malnutrition and long-term outcomes is cognitive development. However, there is limited empirical evidence on the relationship between nutritional status and cognitive achievement in middle childhood.Study designAs part of the South India Community Health Study (SICHS), we collected educational attainment and anthropometric data from 1,194 children in rural Vellore district of Tamil Nadu, India, and assessed their math and reading skills. We analyzed the relationship between continuous and binary anthropometric measures of nutritional status and three measures of cognitive achievement (reading, math, and grade level), adjusting for potential confounders, using a regression framework.ResultsLower height-for-age and weight-for-age and their corresponding binary measures (stunting, underweight) were associated with lower reading scores, lower math scores, and lower grade level, with the exception of the association between weight-for-age and reading, which was marginally significant. A stunted child had one-third of a grade disadvantage compared to a non-stunted counterpart, whereas an underweight child had one-fourth of a grade disadvantage compared to a non-underweight counterpart. Lower BMI-for-age was associated with grade level and marginally associated with lower math scores, and its binary measure (thinness) was marginally associated with lower math scores.ConclusionsAcute and chronic malnutrition in middle childhood were negatively associated with math scores, reading scores, and educational attainment. Our study provides new evidence that cognitive achievement during middle childhood could be an important mechanism underlying the association between early-life malnutrition and long-term wellbeing.

Background Polyarthritis is common to both mixed connective tissue disease (MCTD) and systemic lupus erythematosus (SLE). Apart from being erosive and deforming in the former, we speculated that it was more common and the extent of joints involved would be higher in MCTD. Methods This was a cross-sectional study that included patients with MCTD aged 18–75 years fulfilling the Kasukawa criteria. An equal number of patients with SLE matched for disease duration and gender were included. Clinical manifestations were compared between patients with MCTD and with SLE. Examination of joints was done for the presence of tenderness or swelling and deformity. Musculoskeletal ultrasound was done on the non-dominant hand for detection of synovitis and tenosynovitis and radiographs of the hands were obtained. The use of methotrexate and non-steroidal anti-inflammatory drugs (NSAIDs) for arthritis was noted. Statistical tests used were non-parametric. Results Forty patients with MCTD and forty patients with SLE were included in this study, with patients being slightly older in MCTD than SLE (36 ± 10.2, 31.8 ± 13.3 years, p = 0.01). There were no significant differences in disease duration (4.7 ± 3.1, 3.7 ± 2.3, p = 0.1) or gender (females = 38, 38). Nearly one-half of patients with MCTD had at least one swollen joint compared with only 15% of patients with SLE. Median (95% confidence interval) tender joint count (5 (4.8–10.4), 0 (1.3–7.2), p = 0.01) and swollen joint count (0 (0.9–2.6), 0 (0–1.2), p = 0.002) was significantly higher in patients with MCTD compared with SLE. More patients with MCTD than SLE had tender or swollen proximal interphalangeal joints (12, 4, p = 0.025). More patients with MCTD than SLE had received methotrexate (8,2, p = 0.04) and NSAIDs (39, 32, p = 0.03) for arthritis. There was no difference in the number of patients with MCTD or SLE who had evidence of synovitis or tenosynovitis on ultrasound. There was no difference in erosive disease on hand radiographs, but acro-osteolysis was higher among MCTD patients. Conclusions A higher proportion of patients with MCTD had at least one swollen and tender joint as compared with patients with SLE, as well as higher use of methotrexate and NSAIDs. However, there was no difference in ultrasound detected synovitis or tenosynovitis.

Epstein-Barr virus (EBV) is involved in the development of a wide range of B cell lympho-proliferative disorders. Its association with plasma cell disorders (PCD) however is not clear, especially in immunocompetent patients. To explore any relationship, 39 patients of suspected PCD with positive M-band on electrophoresis and 50 healthy controls were enrolled. EBV DNA in peripheral blood was quantified using quantitative Real Time Polymerase Chain Reaction (qPCR). Of 39 patients, 15 (38.5%) had EBV DNA compared to 8/50 (16%) controls (p = 0.0008). The mean viral copy number was found to be significantly high in patients compared to controls (1.8 × 105; range = 2.6 × 103–7.6 × 105 copies/ml and 1.7 × 104; range = 7.0 × 102–6.1 × 104 copies/ml respectively; p = 0.003). This is the first study, which characterizes the frequency of EBV in circulation in patients of PCD. The significance of increased prevalence of circulating EBV and a higher viral load in our immunocompetent patients however, needs further evaluation.

There is a paucity of literature on renal diseases associated with HIV infection in Asian countries. Renal disease in HIV-infected children can involve the glomerulus, interstitium, tubules or blood vessels of the kidney. In this case series, five HIV-infected children with various forms of renal disease are reported. The renal pathology included HIV-associated nephropathy, collapsing focal segmental glomerulosclerosis without tubular changes, tubule-interstitial nephritis and minimal change disease (MCD). Case five fulfilled the classification criteria for childhood polyarteritis nodosa (PAN). It is important to screen all HIV-infected children for renal disease to enable detection at an early stage.

Skin is commonly affected by vasculitic process and often subjected to biopsy. Cutaneous vasculitis can be either primary or part of a systemic vasculitic process. This study was conducted to evaluate the diagnostic utility of direct immunofluorescence (DIF) in determination of etiology of cutaneous vasculitis. All histologically proven cases of cutaneous vasculitis over the past two and half years were retrospectively analyzed along with their clinical and DIF findings (IgG, IgA, IgM, and C3). Within this study period, a total of 198 cases of small-vessel vasculitis were diagnosed based on skin biopsy and DIF findings. The mean age of patients was 31.2 years (range 1-84 years) with slight male dominance (M:F ratio 1.06:1). Henoch-Schonlein purpura/IgA vasculitis was the commonest clinical diagnosis (31%), followed by urticarial vasculitis (11%) and others. Idiopathic vasculitis was suspected in 33% cases. Overall, DIF was positive in 60% (119/198) cases, with vascular deposition of IgA being commonest, followed by C3. The clinical diagnosis of Henoch-Schonlein purpura could be confirmed in 61.5% (40/65) cases by DIF, whereas another 20 unsuspected cases were picked up as IgA vasculitis based on DIF findings. DIF findings confirmed lupus vasculitis in 50% cases. Other cases showed variable nonspecific deposition of C3 and IgM in 42% cases. DIF can be highly useful to classify cutaneous vasculitis, with maximum efficacy for diagnosis of IgA vasculitis and lupus vasculitis. It can aid in the accurate diagnosis even when the histological changes are minimal. All cases of suspected cutaneous vasculitis should be subjected to DIF.

The objective of this study was to evaluate the oxidant and antioxidant status in living donor renal allograft transplant recipients. Ninety-two renal transplant recipients with mean age of 34.75 ± 11.22 years were included in the present study. Venous samples of the recipients were drawn: before the transplant (baseline), 5 min after reperfusion, and 2 weeks after transplant. Samples were processed for the measurement of markers of oxidant and antioxidant status viz. malondialdehyde, catalase, glutathione peroxidase, reduced glutathione, ascorbic acid, and total antioxidant system. The mean baseline levels of reduced glutathione, ascorbic acid, and total antioxidant system were 1.61 ± 0.84 mg/g hemoglobin, 3.64 ± 1.49 mg/dL, and 1.42 ± 0.14 mmol/L which decreased at 5 min after reperfusion to 1.32 ± 0.72 (p = 0.010), 2.96 ± 1.25 (p = 0.002), and 1.36 ± 0.12 (p = 0.042), respectively. The malondialdehyde levels increased from a baseline value of 3.11 ± 1.02 µmol/mL to 3.32 ± 1.09 at 5 min after reperfusion (p = 0.344) and 4.01 ± 1.21 (p = 0.000) at 2 weeks. Glutathione peroxidase level decreased from 68.59 ± 32.79 units/g hemoglobin (baseline) to 63.65 ± 32.92 at 5 min after reperfusion (p = 0.530) and increased significantly at 2 weeks to 86.38 ± 37.18 (p = 0.00). There was no significant change in the catalase level. In living donor renal transplantation, oxidative stress starts after reperfusion and is reflected by fall in antioxidant factors and enzymes in the early period. Over the next 2 weeks, there is increased oxidative stress and simultaneous strengthening of antioxidant system which is implied by increase in malondialdehyde and improvement in the markers of antioxidant status.

Human papillomavirus (HPV) is a proven etiological agent for cervical cancer However, not all HPV infections result in cervical cancer. The mechanisms of host immune system to prevent/control HPV infection remain poorly understood. Toll-like receptors (TLRs) are a system of innate immune defense. HPV has been demonstrated to modulate TLR expression and interfere in TLR signaling pathways, leading to persistent viral infection and carcinogenesis. The aim was to study the relative gene expression of TLRs in cervical squamous cell carcinoma (SCC).Gene expression profile of TLRs 1 to 9 was examined in 30 cervical SCCs and an equal number of normal cervical tissue samples using a PCR array platform. Gene expression studies for TLRs 3 and 7 were validated by western blotting.HPV was detected in all cases and in none of the controls (p0.0001). HPV16 was the preponderant (83.3%) subtype. A significant downregulation in the relative gene expression of TLR3 (p0.0001), TLR4 (p0.0005) and TLR5 (p0.0001) was observed in cases. A significant upregulation for TLR1 was observed (p=0.006). Although TLRs 2, 7, 8 and 9 were upregulated and TLR6 was downregulated, it was not significant. The western blot performed with antibodies against TLRs 3 and 7 confirmed the findings of the gene expression studies.A significant downregulation in the gene expression of TLRs 3, 4 and 5 and upregulation of TLR1 was observed in cervical SCC as compared to controls. Study results evoke the proposition for investigating TLRs 3, 4 and 5 agonists for therapeutic exploration.

There is a strong evidence in the literature that human odor is unique to an individual; therefore, the focus of this study was to strengthen this evidence through the testing of sweat samples on unrelated individuals with the same ethnicity. Sweat samples were collected from 42 unrelated Indian males and females residing in the same city to determine the chemical constituents in human sweat. The volatile compounds of sweat were subsequently analyzed and identified using gas chromatography-mass spectrometry, and a National Institute of Standards and Technology library was used for individual profiling. A total of 78 compounds were identified in human sweat tested with 22 compounds found to be unique to the individual (frequency of occurrence one). A scent profile, or "chexmotype," unique to the sweat of each individual was obtained. This is the first extensive study on an Indian population with 36 new compounds detected in human sweat.

There is a high prevalence of hepatitis C virus (HCV) infection among immunosuppressed patients including renal transplant recipients. The study investigated serum viral loads for up to 6 months posttransplantation among these patients. Serum viral load was serially monitored using real-time polymerase chain reaction (PCR) in 25 HCV-positive renal transplant recipients pretransplantation as well as day 10 and 6 months posttransplantation. A liver biopsy specimen obtained under vision at the time of transplantation was analyzed for viral load as well as for histological changes. There was increased viremia at day 10 followed by a significant (2 log) reduction at 6 months posttransplantation. Pretransplantation serum and intrahepatic viral load showed significant positive correlations (r = 0.727; P = .001), the latter also reflecting liver fibrosis score (r = 0.423; P = .05). The findings suggested that serum viral load reflects intrahepatic viral load, which in turn correlates with liver fibrosis. At 6 months posttransplantation, the modulatory effects of immunosuppressive drugs and of the host immune response may lead to a reduced viral load.

Objective We compared levels of Th1/Th2/Th17 cytokines and T-regulatory cells in active and remitting granulomatosis with polyangiitis (GPA). Methodology Twenty-one cases of GPA in active state as well as in remitting state and 20 healthy controls (HC) were enrolled in the study. Cytokines were detected in culture supernatants of PBMCs after stimulation with proteinase-3 (PR3) and phytohemagglutinin antigen (PHA). Serum IL-17 cytokine was studied by ELISA. T-regulatory cells (Tregs) were analyzed by flow cytometry. Gene expression of FOXP3 and ROR-γt was compared by Real Time PCR. Results We observed significantly increased level of IL-17 in serum as well in culture supernatants of PBMCs after PR3 stimulation along with ROR-γt gene expression in active disease state of GPA as compared to HC. Importantly, remitting state showed low levels of serum IL-17 with decreased ROR-γt gene expression and increased FOXP3 expression. Using PR3 as an immunostimulant, we could demonstrate the generation of IL-17 and TNF-α secreting effector memory cells during remission. Reduced FOXP3 expression with reduced IL-10 levels in active disease indicated the reduced function of Tregs in active disease. Conclusion We observed Th17 dominant environment in peripheral blood of patients in active state of disease, with “hyporesponsiveness”, in, in vitro stimulated PBMC-in their ability to secrete TNF-α and IL-6. Treg numbers were unaltered but function was compromised. Targeting PR3 specific effector memory cells, to prevent relapse, and instituting anti IL-17 therapy, or modulating Tregs could be newer forms of therapy for this serious autoimmune disease.

Cryptococcal meningitis in immunocompetent post-partum women has been rarely reported. Immune restoration during post-partum period leads to unmasking of many opportunistic infections that may have been acquired during pregnancy but manifest itself in the post-partum period due to immune reconstitution inflammatory syndrome. This case highlights the importance of considering opportunistic pathogens in immunocompetent patients who may be undergoing immune restoration. We report here a fatal case of post-partum immunocompetent women who presented with clinical features of meningitis. Prognosis of the cryptococcal meningitis not only depends on the immune status of the patient but also on how early the disease is diagnosed in the course of illness.

Summary Glomerular diseases of the transplanted kidney are the most important cause of poor long- term outcome. The estimation of the magnitude of this problem and an elucidation of pathogenic mechanism is essential for improvement of graft survival. This study from the Indian subcontinent aims (i) to determine the incidence of transplant glomerulopathy (TG) and thrombotic microangiopathy (TMA) in a large cohort of indicated renal transplant biopsies, (ii) to evaluate the histological and ultrastructural features of TG and TMA, and (iii) to assess the relationship between the two glomerular lesions. Of a total of 1792 indication renal transplant biopsies received over 5 years (2006–2010), 266 biopsies (of 249 patients) had significant glomerular pathology and were further analyzed along with immunofluorescence, electron microscopy (EM), and C4d immunohistochemistry. TG is the most common glomerular lesion followed by TMA seen in 5.97% and 5.08% of allograft biopsies, respectively, which constitutes 40.23% and 34.2% of biopsies with significant glomerular lesions. Pathologic antibody-mediated rejection (AMR) is associated with both TG and TMA in 71% and 46.5%, respectively. A coexistent TG was found in 18.4% of biopsies with TMA. Endothelial swelling with subendothelial widening, a feature of TMA, is also seen in early TG by EM. Our findings support the concept that TG evolves from a smoldering TMA of various causes.

Chronic granulomatous disease (CGD) results from an inherited defect in the phagocytic cells of the immune system. It is a genetically heterogenous disease caused by defects in one of the five major subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. There is a paucity of data from India on CGD. We herein describe the clinical features in 17 children with CGD from a single tertiary referral center in India. A detailed analysis of the clinical features, laboratory investigations and outcome of 17 children 7 with X-linked (XL) and 10 with autosomal recessive (AR) form was performed. Diagnosis of CGD was based on an abnormal granulocyte oxidative burst evaluated by either Nitroblue Tetrazolium (NBT) test or flow cytometry based Dihyrorhodamine 123 assay or both. The molecular diagnosis was confirmed by genetic mutation analysis in 13 cases. The mean age at diagnosis and the age at onset of symptoms was significantly lower in children diagnosed with XL- CGD compared those with AR disease. Mutations were detected in CYBB gene in 6 patients with XL-CGD and NCF-1 gene mutations were observed in 7 cases of AR- CGD. The course and outcome of the disease was much worse in children diagnosed with X-linked form of disease compared to AR forms of the disease; 4/7 (57%) children with X-CGD were dead at the time of data analysis. This is one of the largest series on chronic granulomatous disease from any developing country.

Currently, in India, the National AIDS Control Organization does not recommend HIV screening for all patients attending health care facilities. The objective of study was to evaluate cost and benefits of opt-out HIV testing at a tertiary care hospital from India. This is a retrospective cohort study of patients who had undergone HIV testing. The cost for HIV testing and cost per HIV-infected patient were determined. A total of 6512 patients (66.4% men and 905 patients younger than 14 years) with mean (SD) age of 30.3 (20.7) years were tested for HIV infection during the study period. Overall, 137 (2.1%) patients tested positive for HIV infection. Total cost for performing HIV tests during study period was Indian Rupees (INR) 649,319 (US dollar [USD] 11805.8). The estimated cost per person tested was INR 99.71 (USD1.8) and cost per HIV-infected patient identified and referred to the antiretroviral therapy centre was INR 4739.55 (USD86.2). We determined a 2.1% period prevalence estimate for HIV infection. Based on cost per HIV-infected patient identified and referred to the antiretroviral therapy centre and the burden of HIV infection, it may be cost effective to perform routine opt-out screening for HIV infection in all patients attending health care facilities in developing countries like India.

Henoch-Schönlein purpura (HSP) is an acute systemic vasculitis with unknown etiology, although several studies have found HSP to be related to cytokines such as tumor necrosis factor α, interleukin (IL)-1, and adhesion molecules. In the present study we determined the levels of cytokines such as IL-18 and endothelin-1 (ET-1) in children with HSP. Subjects were divided into three groups (group 1, 20 subjects with HSP; group 2, 10 subjects belonging to group 1 during their follow-up 4 to 6 months later; and group 3, 16 controls who were healthy siblings of the subjects). IL-18 and ET-1 levels were determined using enzyme immunoassay and expressed as mean ± standard deviation. We observed higher IL-18 levels in children with HSP (767.6 ± 145.1 pg/mL) than in controls (614.6 ± 66.54 pg/mL, p 0.05), but IL-18 levels were found to be significantly lower in subjects with HSP in remission (502.7 ± 60.81 pg/mL) than in those who were in an active phase (1,050 ± 244.5 pg/mL, p 0.05, n = 10). ET-1 levels were found to be significantly higher in subjects with HSP (1.93 ± 0.19 pg/mL) than in controls (1.10 ± 0.13 pg/mL, p 0.05), although no significant difference was observed in ET-1 levels between subjects in group 1 (1.88 ± 0.30 pg/mL) and group 2 (1.91 ± 0.120, p 0.05, n = 10). A positive correlation was observed between IL-18 and ET-1 levels in subjects with HSP (correlation coefficient [r] = 0.5254, p 0.01). These results suggest that levels of IL-18 and ET-1 are worth monitoring during the clinical course of the disease, but caution must be exercised in extrapolating data based on small study samples.