Other articles by Sampath Prahalad on PubMed

• Increased Prevalence of Familial Autoimmunity in Simplex and Multiplex Families with Juvenile Rheumatoid Arthritis Arthritis and Rheumatism. Jul, 2002  |   Pubmed ID: 12124869 To determine if the prevalence of autoimmunity among relatives of patients with juvenile rheumatoid arthritis (JRA) is greater than that among relatives of healthy volunteer control subjects.
• Lack of Association Between Birth Order and Juvenile Idiopathic Arthritis Arthritis and Rheumatism. Oct, 2003  |   Pubmed ID: 14558107
• Genetics of Juvenile Idiopathic Arthritis: an Update Current Opinion in Rheumatology. Sep, 2004  |   Pubmed ID: 15314499 Juvenile idiopathic arthritis (JIA) refers to a collection of chronic arthritides in children, and the major subtypes of JIA are similar to the subtypes of juvenile rheumatoid arthritis (JRA). Several genetic variants influencing susceptibility to JIA have been identified, including genes encoding the HLA molecules, cytokines, and other modulators of immune responses. This review outlines the principles behind genetic studies and summarizes recent studies on the genetics of JIA.
• A Genome-wide Scan for Juvenile Rheumatoid Arthritis in Affected Sibpair Families Provides Evidence of Linkage Arthritis and Rheumatism. Sep, 2004  |   Pubmed ID: 15457461 Juvenile rheumatoid arthritis (JRA) represents a heterogeneous group of disorders with a complex genetic component. A genome scan was performed to detect linkage to JRA in 121 families containing 247 affected children in North America (the JRA Affected Sibpair [ASP] Registry).
• Idiopathic Hypercalcemia and Eosinophilic Fasciitis: a Novel Association Journal of Pediatric Endocrinology & Metabolism : JPEM. Sep, 2004  |   Pubmed ID: 15506687 A 15 year-old boy presented with moderate hypercalcemia (serum calcium 3.35 mmol/l) and eosinophilic fasciitis. An extensive search for a cause of hypercalcemia or underlying malignancy proved negative. Glucocorticoid treatment resulted in significant clinical improvement and resolution of the hypercalcemia. This report describes the novel association of hypercalcemia with eosinophilic fasciitis, with potential implications for the role of inflammatory mediators.
• Familial Aggregation of Juvenile Idiopathic Arthritis Arthritis and Rheumatism. Dec, 2004  |   Pubmed ID: 15593218 To estimate the degree of familial aggregation of juvenile idiopathic arthritis (JIA), determine whether the aggregation of JIA and the aggregation of type 1 diabetes mellitus (type 1 DM) overlap, and identify multiplex JIA pedigrees.
• Fatal Acute Fibrinous and Organizing Pneumonia in a Child with Juvenile Dermatomyositis The Journal of Pediatrics. Feb, 2005  |   Pubmed ID: 15689928 Acute fibrinous and organizing pneumonia, a recently described form of diffuse acute lung injury, sometimes affects adults with inflammatory myopathy. We describe a child with juvenile dermatomyositis who had development of acute fibrinous and organizing pneumonia. There does not appear to be a successful method of treatment, particularly in severe cases with respiratory failure.
• Tender Point Assessment in Juvenile Primary Fibromyalgia Syndrome Arthritis and Rheumatism. Oct, 2005  |   Pubmed ID: 16208646
• Genetic Analysis of Juvenile Rheumatoid Arthritis: Approaches to Complex Traits Current Problems in Pediatric and Adolescent Health Care. Mar, 2006  |   Pubmed ID: 16473284
• Musculoskeletal Abnormalities of the Tibia in Juvenile Rheumatoid Arthritis Arthritis and Rheumatism. Mar, 2007  |   Pubmed ID: 17328076 To characterize local bone geometry, density, and strength, using peripheral quantitative computed tomography (pQCT), compared with general bone characteristics as measured using dual x-ray absorptiometry (DXA), and to assess their relationship to disease-related factors in children with juvenile rheumatoid arthritis (JRA).
• Familial Autoimmunity: Maternal Parent-of-origin Effect in Juvenile Idiopathic Arthritis Clinical Rheumatology. Feb, 2008  |   Pubmed ID: 17994193 Juvenile idiopathic arthritis (JIA) is an autoimmune (AI) disease characterized by chronic arthritis in children. Children with JIA have increased prevalence of other AI diseases. Furthermore, relatives of children with JIA have been shown to have an increased prevalence of AI diseases. Our objective was to determine if there were differences in the prevalence of AI diseases among maternal and paternal relatives of children with JIA. Information about AI diseases among all living first- and second-degree relatives was collected by structured interviews with families of 121 simplex JIA families, 23 multiplex JIA families, and 45 control families. Overall, the prevalence of AI diseases was significantly increased among maternal second-degree relatives of cases compared to that of maternal second-degree relatives of controls [14% vs. 4.3%; p < 0.001]. The prevalence of AI diseases among mothers of JIA cases was three times that of fathers [32.3% vs. 11.4%; p < 0.0001]. The prevalence of AI diseases among all maternal second-degree relatives of children with JIA was significantly higher than that of all paternal second-degree relatives [14% vs. 7.9%; p < 0.004]. Although additional paternal effects cannot be excluded, together these results demonstrate that maternal relatives of children with JIA have an increased prevalence of autoimmunity compared to paternal relatives, suggesting that there might be a maternal parent-of-origin effect in JIA.
• Elevated Serum Levels of Soluble CD154 in Children with Juvenile Idiopathic Arthritis Pediatric Rheumatology Online Journal. 2008  |   Pubmed ID: 18507862 Cytokines play important roles in mediating inflammation in autoimmunity. Several cytokines are elevated in serum and synovial fluid samples from children with Juvenile Idiopathic Arthritis (JIA). Soluble CD154 (sCD154) is elevated in other autoimmune disorders, but has not been characterized in JIA. Our objectives were to determine if sCD154 is elevated in JIA, and to examine correlations between sCD154 and other inflammatory cytokines.
• Lack of Association of Functional CTLA4 Polymorphisms with Juvenile Idiopathic Arthritis Arthritis and Rheumatism. Jul, 2008  |   Pubmed ID: 18576317 Juvenile idiopathic arthritis (JIA) is an autoimmune disorder mediated by Th1 immune responses. CTLA-4, expressed on the T cell surface, plays a negative role in regulating T cell activation. Single-nucleotide polymorphisms (SNPs) in CTLA4 have been implicated in susceptibility to several autoimmune disorders, including JIA. This study was undertaken to test 3 functional CTLA4 variants for association with JIA.
• A Comprehensive Review of the Genetics of Juvenile Idiopathic Arthritis Pediatric Rheumatology Online Journal. 2008  |   Pubmed ID: 18644131 Juvenile idiopathic arthritis (JIA) is the most common chronic arthropathy of childhood which is believed to be influenced by both genetic and environmental factors. The progress in identifying genes underlying JIA susceptibility using candidate gene association studies has been slow. Several associations between JIA and variants in the genes encoding the human leukocyte antigens (HLA) have been confirmed and replicated in independent cohorts. However it is clear that genetic variants outside the HLA also influence susceptibility to JIA. While a large number of non-HLA candidate genes have been tested for associations, only a handful of reported associations such as PTPN22 have been validated. In this review we discuss the principles behind genetic studies of complex traits like JIA, and comprehensively catalogue non-HLA candidate-gene association studies performed in JIA to date and review several validated associations. Most candidate gene studies are underpowered and do not detect associations, and those that do are often not replicated. We also discuss the principles behind genome-wide association studies and discuss possible implications for identifying genes underlying JIA. Finally we discuss several genetic variants underlying multiple clinically distinct autoimmune phenotypes.
• Genome-wide Scan Reveals Association of Psoriasis with IL-23 and NF-kappaB Pathways Nature Genetics. Feb, 2009  |   Pubmed ID: 19169254 Psoriasis is a common immune-mediated disorder that affects the skin, nails and joints. To identify psoriasis susceptibility loci, we genotyped 438,670 SNPs in 1,409 psoriasis cases and 1,436 controls of European ancestry. We followed up 21 promising SNPs in 5,048 psoriasis cases and 5,041 controls. Our results provide strong support for the association of at least seven genetic loci and psoriasis (each with combined P < 5 x 10(-8)). Loci with confirmed association include HLA-C, three genes involved in IL-23 signaling (IL23A, IL23R, IL12B), two genes that act downstream of TNF-alpha and regulate NF-kappaB signaling (TNIP1, TNFAIP3) and two genes involved in the modulation of Th2 immune responses (IL4, IL13). Although the proteins encoded in these loci are known to interact biologically, we found no evidence for epistasis between associated SNPs. Our results expand the catalog of genetic loci implicated in psoriasis susceptibility and suggest priority targets for study in other auto-immune disorders.
• Health-related Quality of Life of Patients with Juvenile Dermatomyositis: Results from the Pediatric Rheumatology International Trials Organisation Multinational Quality of Life Cohort Study Arthritis and Rheumatism. Apr, 2009  |   Pubmed ID: 19333974 To investigate the health-related quality of life (HRQOL) change over time, as measured by the Child Health Questionnaire (CHQ), and its determinants in patients with active juvenile dermatomyositis (DM).
• Anakinra for Systemic Juvenile Arthritis: the Rocky Mountain Experience Journal of Clinical Rheumatology : Practical Reports on Rheumatic & Musculoskeletal Diseases. Jun, 2009  |   Pubmed ID: 19363453 Poor outcomes in systemic juvenile arthritis have been associated with persistent thrombocytosis, increased sedimentation rates, anemia, polyarthritis, and prolonged steroid use. Off-label treatment with recombinant interleukin-1 receptor antagonist therapy (anakinra) has become more common since reports of its association with reduced systemic symptoms and arthritis scores, improved laboratory parameters of inflammation, and decreased corticosteroid requirements.
• Variants in TNFAIP3, STAT4, and C12orf30 Loci Associated with Multiple Autoimmune Diseases Are Also Associated with Juvenile Idiopathic Arthritis Arthritis and Rheumatism. Jul, 2009  |   Pubmed ID: 19565500 Subtypes of juvenile idiopathic arthritis (JIA) share phenotypic features with other autoimmune disorders. We investigated several genetic variants associated with rheumatoid arthritis (RA) and other autoimmune disorders for association with JIA to test the hypothesis that clinically distinct phenotypes share common genetic susceptibility factors.
• The Genetics of Juvenile Idiopathic Arthritis: What is New in 2010? Current Rheumatology Reports. Apr, 2010  |   Pubmed ID: 20425016 Juvenile idiopathic arthritis (JIA), the most common cause of chronic arthritis in children, is believed to be influenced by genetic factors. Recent studies on the genetics of JIA have not only validated proposed genetic associations but have also led to the recognition of novel genetic associations. Studies of specific genes have been modeled on the premise of shared autoimmunity, wherein genetic variants that predispose to other autoimmune phenotypes may also confer susceptibility to JIA. The advent of genome-wide association studies has accelerated the detection of non-HLA susceptibility loci in other autoimmune phenotypes and is likely to uncover novel JIA-associated variants as well. This review highlights recent genetic investigations of JIA.
• Quantification of the Familial Contribution to Juvenile Idiopathic Arthritis Arthritis and Rheumatism. Aug, 2010  |   Pubmed ID: 20506132 We previously demonstrated that there is familial aggregation of juvenile idiopathic arthritis (JIA). Using a large JIA cohort, we sought to identify additional clusters of JIA cases and to calculate robust estimates of the relative risk (RR) of JIA in the siblings and cousins of JIA probands. We also estimated the population attributable risk (PAR) of familial factors in JIA.
• The Susceptibility Loci Juvenile Idiopathic Arthritis Shares with Other Autoimmune Diseases Extend to PTPN2, COG6, and ANGPT1 Arthritis and Rheumatism. Nov, 2010  |   Pubmed ID: 20722033 To test for associations between non-major histocompatibility complex susceptibility loci previously reported in autoimmune diseases and juvenile idiopathic arthritis (JIA).
• Development of a Vision-related Quality of Life Instrument for Children Ages 8-18 Years for Use in Juvenile Idiopathic Arthritis-associated Uveitis Arthritis Care & Research. Sep, 2011  |   Pubmed ID: 21678564 To determine the validity and reliability of a novel questionnaire to measure vision-related quality of life (VRQOL) in children ages 8-18 years for use in juvenile idiopathic arthritis (JIA)-associated uveitis: the Effects of Youngsters' Eyesight on Quality of Life (EYE-Q).
• Evaluation of Genetic Association Between an ITGAM Non-synonymous SNP (rs1143679) and Multiple Autoimmune Diseases Autoimmunity Reviews. Feb, 2012  |   Pubmed ID: 21840425 Many autoimmune diseases (ADs) share similar underlying pathology and have a tendency to cluster within families, supporting the involvement of shared susceptibility genes. To date, most of the genetic variants associated with systemic lupus erythematosus (SLE) susceptibility also show association with others ADs. ITGAM and its associated 'predisposing' variant (rs1143679, Arg77His), predicted to alter the tertiary structures of the ligand-binding domain of ITGAM, may play a key role for SLE pathogenesis. The aim of this study is to examine whether the ITGAM variant is also associated with other ADs. We evaluated case-control association between rs1143679 and ADs (N=18,457) including primary Sjögren's syndrome, systemic sclerosis, multiple sclerosis, rheumatoid arthritis, juvenile idiopathic arthritis, celiac disease, and type-1 diabetes. We also performed meta-analyses using our data in addition to available published data. Although the risk allele 'A' is relatively more frequent among cases for each disease, it was not significantly associated with any other ADs tested in this study. However, the meta-analysis for systemic sclerosis was associated with rs1143679 (p(meta)=0.008). In summary, this study explored the role of ITGAM in general autoimmunity in seven non-lupus ADs, and only found association for systemic sclerosis when our results were combined with published results. Thus ITGAM may not be a general autoimmunity gene but this variant may be specifically associated with SLE and systemic sclerosis.
• Hierarchy of Risk of Childhood-onset Rheumatoid Arthritis Conferred by HLA-DRB1 Alleles Encoding the Shared Epitope Arthritis and Rheumatism. Mar, 2012  |   Pubmed ID: 21953520 Associations between shared epitope (SE)-encoding HLA-DRB1 alleles and rheumatoid arthritis (RA) are well established. However, only a limited number of studies have investigated these alleles in patients with childhood-onset RA, which is defined as rheumatoid factor- and/or anti-citrullinated protein antibody-positive juvenile idiopathic arthritis. The aims of this study were to investigate the largest cohort of patients with childhood-onset RA for association with SE alleles and to determine whether there is a hierarchy of risk based on the amino acid sequence of the SE.
• Consensus Treatment Plans for New-onset Systemic Juvenile Idiopathic Arthritis Arthritis Care & Research. Jul, 2012  |   Pubmed ID: 22290637 There is wide variation in therapeutic approaches to systemic juvenile idiopathic arthritis (JIA) among North American rheumatologists. Understanding the comparative effectiveness of the diverse therapeutic options available for treatment of systemic JIA can result in better health outcomes. The Childhood Arthritis and Rheumatology Research Alliance (CARRA) developed consensus treatment plans and standardized assessment schedules for use in clinical practice to facilitate such studies.
• Genome-wide Association Analysis of Juvenile Idiopathic Arthritis Identifies a New Susceptibility Locus at Chromosomal Region 3q13 Arthritis and Rheumatism. Aug, 2012  |   Pubmed ID: 22354554 In a genome-wide association study of Caucasian patients with juvenile idiopathic arthritis (JIA), we have previously described findings limited to autoimmunity loci shared by JIA and other diseases. The present study was undertaken to identify novel JIA-predisposing loci using genome-wide approaches.
• Profiling Anti-cyclic Citrullinated Peptide Antibodies in Patients with Juvenile Idiopathic Arthritis Pediatric Rheumatology Online Journal. 2012  |   Pubmed ID: 22931121 Anti-citrullinated protein/peptide antibodies (ACPA), have high specificity for rheumatoid arthritis (RA). Some children with juvenile idiopathic arthritis (JIA), phenotypically resemble RA and test positive for rheumatoid factor (RF) a characteristic biomarker of RA. We investigated the prevalence of ACPA and its relationship to other serologic markers associated with RA in a well-characterized JIA cohort.
• Susceptibility to Childhood Onset Rheumatoid Arthritis: Investigation of a Weighted Genetic Risk Score That Integrates Cumulative Effects of Variants at Five Genetic Loci Arthritis and Rheumatism. Feb, 2013  |   Pubmed ID: 23450725 OBJECTIVES: Children with rheumatoid-factor or anti-citrullinated peptide antibody positive juvenile idiopathic arthritisrepresent the childhood onset of RA (CORA). To test the hypothesis that adult-onset RA-associated variants are also associated with CORA, we investigated RA-associated variants at five loci in ourCORA cohort. We also assessedthe cumulative association of these variants in the susceptibility to CORA using aweighted genetic risk score (wGRS). METHODS: 155 children with CORA and 684healthy controls were genotyped for fivevariants in PTPN22, TRAF1/C5, STAT4, and TNFAIP3 loci. High-resolution HLA-DRB1 genotypes were available for149 cases and 373 controls. We testedeach locus for associationwith CORA via logistic regression. Wealso computed a wGRS for each subject, with weights based on the natural log of the published odds ratios for the alleles investigated, and used logistic regression to test the wGRS for association with CORA. RESULTS: CORA was associated withTNFAIP3-rs10499194 [OR 0.60 (95%CI 0.44-0.83)], PTPN22-rs2476601 [OR 1.61 (1.11-2.31)], and STAT4-rs7574865 [OR 1.41 (1.06-1.87)] variants. The wGRS was significantly different between cases and controls (P
• Dense Genotyping of Immune-related Disease Regions Identifies 14 New Susceptibility Loci for Juvenile Idiopathic Arthritis Nature Genetics. Apr, 2013  |   Pubmed ID: 23603761 We used the Immunochip array to analyze 2,816 individuals with juvenile idiopathic arthritis (JIA), comprising the most common subtypes (oligoarticular and rheumatoid factor-negative polyarticular JIA), and 13,056 controls. We confirmed association of 3 known JIA risk loci (the human leukocyte antigen (HLA) region, PTPN22 and PTPN2) and identified 14 loci reaching genome-wide significance (P < 5 × 10(-8)) for the first time. Eleven additional new regions showed suggestive evidence of association with JIA (P < 1 × 10(-6)). Dense mapping of loci along with bioinformatics analysis refined the associations to one gene in each of eight regions, highlighting crucial pathways, including the interleukin (IL)-2 pathway, in JIA disease pathogenesis. The entire Immunochip content, the HLA region and the top 27 loci (P < 1 × 10(-6)) explain an estimated 18, 13 and 6% of the risk of JIA, respectively. In summary, this is the largest collection of JIA cases investigated so far and provides new insight into the genetic basis of this childhood autoimmune disease.
• Evaluation of the Association Between Hispanic Ethnicity and Disease Activity and Severity in a Large Cohort of Patients with Juvenile Idiopathic Arthritis Rheumatology International. May, 2013  |   Pubmed ID: 23660749 To examine the association between ethnicity and disease activity in patients with juvenile idiopathic arthritis (JIA), and to determine the association of ethnicity with disease severity and disability in this population. CARRAnet, a US database containing information (collected between May 2010 and June 2011) on almost 3,000 subjects with JIA, was used. Demographic variables were compared between Hispanic patients and non-Hispanic patients. Mann-Whitney and chi-square tests were used to compare indicators of disease activity, as well as imaging evidence of joint damage, and Childhood Health Assessment Questionnaire (CHAQ) scores between ethnicities. Two linear regression models were used to determine the association of ethnicity with number of active joints in JIA, and the association between ethnicity and disability (CHAQ scores). A total of 2,704 patients with JIA (277 Hispanic; 2,427 non-Hispanic) were included. Income and health insurance coverage were higher in non-Hispanics. RF-positive polyarticular JIA, positive RF and anti-CCP, as well as use of systemic steroids were more frequent in Hispanics. Imaging evidence of joint damage was present in 32 % of the Hispanic patients compared to 24 % of the non-Hispanic patients (p = 0.008). In multivariate linear regression analyses, the number of active joints was significantly higher in Hispanics than in non-Hispanics (p = 0.03), as well as CHAQ scores (p = 0.003), after adjusting for confounders. Hispanic patients with JIA had higher disease activity than non-Hispanic patients, as well as higher disease severity and disability. Since ethnicity influences disease activity, severity, and disability, different management and treatment plans should be planned accordingly.