Reena Gulati

Susceptibility to SLE in South Indian Tamils may be influenced by genetic selection pressure on TLR2 and TLR9 genes.

INTRODUCTION Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder with complex etiology. Genetics plays an important role in lupus pathogenesis through its influence on clinical and autoantibody phenotype of the disease. Toll like receptors (TLR) recognize molecular patterns of pathogens and activate the innate immune system. Their ability to identify nucleic acids makes them suitable candidates for investigation of their role in lupus pathogenesis. Hence, this study was carried out to analyze the G to A and C to T transitions in TLR2 and TLR9 genes respectively and to test their association with lupus susceptibility, clinical and autoantibody phenotypes in South Indian Tamils. METHOD Three hundred SLE patients fulfilling ACR 2012 criteria for SLE and 460 age, sex similar, ethnicity matched controls were recruited as cases and controls. TLR2 (R753Q) and TLR9 (-1237C/T) polymorphisms were analyzed by real time PCR. RESULTS The TLR2 gene remained monomorphic in patients and controls, the frequency of the homozygous wild type allele being 100% and 99.6% respectively. Hence, it did not confer susceptibility to SLE. The more frequent T allele of TLR9 gene conferred a significant risk to develop SLE (p=0.011, OR 1.69, 95% CI 1.1-2.6). Both the polymorphisms did not influence clinical or autoantibody phenotype of the disease. CONCLUSION Prevailing endemic infections in the Indian subcontinent may have exerted a selection pressure resulting in TLR2 gene remaining monomorphic and the TLR9 adapting to a mutation for its increased expression. These may have an additive effect in the presence of other genetic and environmental risk factors to confer susceptibility to SLE in South Indian Tamils.

The CTLA4 +49 A/G (rs231775) polymorphism influences susceptibility to SLE in South Indian Tamils.

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with complex etiology. Loss of immune tolerance and synthesis of autoantibodies against nuclear antigens contributes to the disease. Genetic aberrations disrupting the functions of immune regulatory receptors may facilitate the development of autoimmune diseases. Cytotoxic T-lymphocyte antigen 4 (CTLA4) is an inhibitory receptor for T cells and this study was carried out to analyze the influence of CTLA4 +49A/G (rs231775) polymorphism on susceptibility to SLE in ethnic Tamils. Three hundred SLE patients and 460 age and sex similar, ethnicity-matched controls were screened for the +49 A/G polymorphism by real time polymerase chain reaction (PCR). The wild allele (A) frequency in controls and cases was 63% and 47%, respectively. The presence of heterozygous (AG) and homozygous mutant (GG) genotype was associated with a significant risk to develop SLE (P = 0.0001, OR-2.29, 95% confidence interval (CI), 1.6-3.3) and (P = 0.0001, OR-4.3, 95% CI, 2.8-6.99). The frequency of mutant allele (G) in patients was also significantly associated with SLE (P = 0.0001, OR-1.9, 95% CI, 1.5-2.4). However, this polymorphism did not influence the clinical or serological phenotypes in our study. Therefore the CTLA4 +49 A/G polymorphism is a potential genetic risk factor for lupus susceptibility in South Indian Tamils, but does not appear to influence either the clinical or serological phenotype.

Complement C1q and C2 polymorphisms are not risk factors for SLE in Indian Tamils

INTRODUCTION Complement system is an important effector component of the innate immune system. More than 30 plasma proteins undergo a cascade of enzymatic reactions to produce effector molecules to clear infectious microbes, immune complexes, post apoptotic cellular debris and thus participate in prevention of autoimmunity. Absolute deficiency of individual complement components and selective deficiency of classical pathway complement components are reported to be associated with severe infections and a high risk for lupus like syndromes. Genetic defects in gene encoding for complement components were reported to be associated with complement deficiency. This study was carried out to investigate whether C1q and C2 polymorphisms are risk factors for SLE in south Indian Tamils. MATERIALS AND METHODS Three hundred SLE patients fulfilling ACR criteria for SLE and 460 age and sex similar ethnicity matched individuals were included as patients and healthy controls respectively. The genomic DNA obtained from both the groups was screened for two polymorphisms including a C/T transition in exon 2 of C1qA (rs121909581) by PCR-RFLP and a 28bp deletion in sixth exon of C2 gene by PCR. RESULTS C1q exon 2 C/T polymorphism analysis revealed that homozygous CC was the most common genotype in patients and controls. A single SLE patient was found to have heterozygous variant (CT). None of the patients or healthy controls were found to have 28bp deletion variant of C2 gene. CONCLUSION The C/T polymorphism in exon 2 of C1qA and a 28bp deletion in sixth exon of C2 gene were found to be rare in south Indian Tamil SLE patients. They do not appear to be susceptibility factors for SLE in Indian Tamils.

Immunoglobulin-like transcripts 6 (ILT6) polymorphism influences the anti-Ro60/52 autoantibody status in south Indian SLE patients

Introduction Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder with complex etiology. Loss of immune tolerance against self-antigens results in activation of the immune system to produce autoantibodies, which in turn contribute to the clinical manifestations of the disease. Immune cells harbor a plethora of regulatory receptors. Immunoglobulin-like transcripts (ILTs) exhibit both immune activation and inhibitory properties. Genetic defects in genes encoding these receptors may predispose to development of autoimmune diseases secondary to loss of their function. The aim of our study was to analyze the presence or absence of the 6.7 kb segment in the ILT6 gene and its association with susceptibility to SLE and its different manifestations. Method A total of 188 SLE patients and 192 age-, sex similar-, ethnicity-matched controls were recruited. They were genotyped to test the presence or absence of the 6.7 kb segment of the ILT6 gene by polymerase chain reaction. Results The mutant allele lacking the 6.7 kb gene segment had an equal frequency in patients as well as controls (20% and 18%, respectively). The mutant allele was not associated with SLE or its clinical manifestations. However, the mutant allele was associated with the presence of anti-Ro60 (p = 0.0005, OR 3.5, 95% CI 1.8–7.1) and anti-Ro52 (p = 0.0027, OR 2.99, 95% CI 1.5–6.06) autoantibodies. Conclusion ILT6 deletion polymorphism does not appear to be a lupus susceptibility gene in South Indian Tamils, but may behave as a genetic modifier of autoantibody phenotype by influencing the production of anti-Ro60 and anti-Ro52 autoantibodies and thus indirectly contribute to autoimmune responses in SLE.

Fulminant BCG Disease in a 7 Month Old Healthy Male Infant.

A seven month old healthy male infant was brought with papular skin lesions all over the body, which became ulcerative with increasing fever and redness within 1 week duration. On examination, Bacilli Calmette Guerin (BCG) scar was ulcerated with discharge; infant was irritable with tachycardia and tachypnea. Investigations revealed pancytopenia, and acid fast bacilli was positive in skin lesions and at BCG scar site. There was progressive worsening of infants condition, culminating in death.

Antiphospholipid Syndrome Complicating Pneumococcal Meningitis

BackgroundAntiphospholipid syndrome is a multisystem auto-immune disorder characterized by arterial or venous thrombosis in children.Case characteristics11-year-old child with pneumococcal meningitis also had cerebral sinus vein thrombosis and pulmonary artery segmental thrombosis.ObservationPro-thrombotic evaluation showed positive lupus anticoagulant at baseline and after 12 weeks. Investigations for lupus were negative at admission and after one year of follow-up.MessageAntiphospholipid syndrome is a possibility even in thrombosis occurring in the setting of meningitis.

Nonassociation of homocysteine gene polymorphisms with treatment outcome in South Indian Tamil Rheumatoid Arthritis patients

The aim of the study was to look for any association of MTR 2756A>G and MTRR 66A>G gene polymorphisms with clinical phenotype, methotrexate (MTX) treatment response, and MTX-induced adverse events in South Indian Tamil patients with rheumatoid arthritis (RA). A total of 335 patients with RA were investigated. MTR 2756A>G gene polymorphism was analyzed by PCR–RFLP, and MTRR 66A>G SNP was analyzed by TaqMan 5′ nuclease assay. The allele frequencies were compared with HapMap groups. MTR 2756G allele was found to be associated with risk of developing RA. The allele frequencies of MTR 2756A>G and MTRR 66A>G SNPs in controls differed significantly when compared with HapMap groups. Neither of the SNPs influenced the MTX treatment outcome and adverse effects. Neither of the SNPs seems to be associated with MTX treatment outcome and adverse events in South Indian Tamil patients with RA.

Complicated acute cerebellitis with obstructive hydrocephalus and tonsillar herniation in a child.

Acute cerebellitis (AC) is a rare inflammatory syndrome presenting as cerebellar dysfunction, seen more frequently in children. AC can have a variable course with features of cerebellar dysfunction, raised intracranial pressure and neurological deficits, and can sometimes even be potentially fatal due to complications such as obstructive hydrocephalus and brainstem compression, warranting surgical intervention. We report a case of a 12-year-old boy who presented with raised intracranial pressure and ataxia. Imaging with CT and MRI showed AC with obstructive hydrocephalus and tonsillar herniation. He was managed with medications for raised intracranial pressure and with ventriculoperitoneal shunt, and he recovered completely over a period of 2 weeks. Imaging has an important role in the diagnosis of AC and in differentiating it from acute cerebellar ataxia, which has a more benign course. It is crucial to diagnose and promptly manage the rarely occurring but life-threatening complications of AC.

Persistent tachypnoea in an infant with cystic lung lucencies on CT scan

A 1 year and 8 months old boy, with mild motor developmental delay and right hemiparesis following a perinatal brain injury, was brought with a history of fast breathing and cough for 2 months and low-grade fever of 10 days duration. He was second born to non-consanguineously wed parents by spontaneous vaginal delivery with delayed cry at birth and neonatal intensive care unit stay for 10 days. There was no exposure to cigarette smoke. On examination there was mild central cyanosis with pan digital clubbing; pulse rate was 102 per minute; respiratory rate was 44 per minute; oxygen saturation of 89% which improved to 95% with 2 L/min of oxygen. On systemic examination, cardiovascular status was found to be normal; respiratory examination revealed coarse crepitations bilaterally in the entire lung …

Atlantoaxial dislocation in a patient with nonsyndromic symmetrical dwarfism: Report of a rare case

Congenital anomalies of the craniovertebral junction (CVJ) are complex developmental defects. We describe a patient with atlantoaxial dislocation (AAD) and short stature whose morphopathologydid not fit into any of the previously described syndromic constellations. The patient underwent a reduction of the AAD followed by fixation with C1-C2 transarticular screws. Although numerous syndromes have been linked to both dwarfism and craniovertebral junction anomalies, this patient did not fit into any of these patterns. It is possible that this may be one of the many as yet unrecognized patterns of congenital anomalies.