Background:HLA alleles may have association with overall JIA including specific
sub-types. Determation of HLA DRB1, DPB1, DQA1, DQB1 and B27, may be helpful to
diagnose JIA cases where diagnostic dilemma is present.The aim of the study was to find out the association of HLA alleles with
JIA and its subtypes. Methods: This cross sectional study was conducted
in the department of Pediatrics, Bangabandhu Sheikh Mujib Medical University
(BSMMU), Dhaka, from April 2020 to March 2021. A total of 50 cases and 25controlsattending pediatric rheumatology clinic and
pediatric OPD were enrolled in the study.
Data were collected by a pre-designed questionnaire containing
socio-demographic, clinical and laboratory parameters. HLA DR-B1, DQ-A1, DQ-B1
and B27 typing were done for the cases and controls from blood samples by polymerase chain reaction
sequence specific primer (PCR-SSP)
method. Data were analyzed by SPSS
version 26. Frequency, percentage, chi square test and Fisher exact tests were
done for statistical analysis. Results: HLA DR-B1_10 had significant
positive association whereas HLA DR-B1_03 and B1_16
had negative association with overall JIA cases. Poly-articular JIA,
oligo-articular JIA and ERA had association with HLA DRB1_01, B1_08 and B1_12
respectively. HLA DQA1-01 and A1_02 had positive association. However, DQ-A1_06
was negatively associated with JIA cases. Oligo JIA was positively associated
with HLA DQ-A1_01, whereas poly JIA and ERA had association with A1_02. Though,
HLA DQ_B1 had no association with overall JIA cases, analysis showed
association of poly JIA with DQ-B1_04. Frequency of HLA DQ-B1_02 and 03 were
higher among ERA cases, though not significant, but they had strong association
with HLA B27. Conclusion: HLA associations were present with overall JIA
and each sub-groups had different patterns of HLA associations including some
protective roles.
References
[1]
Kliegman, R. and St. Geme, J. (2020) Nelson Textbook of Prdiatrics. 21st Edition, Saunders Elevier, Philadelphia.
[2]
Mahmud, S.A. and Binstadt, B.A. (2019) Autoantibodies in the Pathogenesis, Diagnosis, and Prognosis of Juvenile Idiopathic Arthritis. Frontiers in Immunology, 9, Article 3168. https://doi.org/10.3389/fimmu.2018.03168
[3]
Murray, K.J., Luyrink, L., Grom, A.A., Passo, M.H., Emery, H., Witte, D., et al. (1996) Immunohistological Characteristics of T Cell Infiltrates in Different Forms of Childhood Onset Chronic Arthritis. A Rheumatology Journal, 23, 2116-2124.
[4]
Hofer, M. and Southwood, T.R. (2002) Classification of Childhood Arthritis. Best Practice & Research Clinical Rheumatology, 16, 379-389.
https://doi.org/10.1053/berh.2002.0235
[5]
Gravito, G., Yunis, E.J., Egea, E., et al. (2004) HLA-DRB1 Alleles and HLA-DRB1 Shared Epitopes Are Markers for Juvenile Rheumatoid Arthritis Subgroups in Colombian Mestizos. Human Immunology, 65, 359-365.
https://doi.org/10.1016/j.humimm.2004.01.016
[6]
Pires, C.F., Londe, A.C.S., Brito, J.J.C., Bertolo, M.B., et al. (2018) Association of HLA DR and DQ with Juvenile Idiopathic Arthritis in Brasilian Piauienses Children. Journal of Molecular and Genetic, 12, Article ID: 1000357.
https://doi.org/10.4172/1747-0862.1000357
[7]
Ploski, R., Vinje, O., Ronningen, K.S., et al. (1993) HLA Class II Alleles and Heterogeneity of Juvenile Rheumatoid Arthritis. drb1*0101 may Define a Novel Subset of the Disease. Arthritis & Rheumatism, 36, 465-472.
https://doi.org/10.1002/art.1780360406
[8]
Prahalad, S., Thompson, S.D., Conneely, K.N., Jiang, Y., Leong, T., et al. (2012) Hierarchy of Risk of Childhood-Onset Rheumatoid Arthritis Conferred by HLA-DRB1 Alleles Encoding the Shared Epitope. Arthritis & Rheumatism, 64, 925-930.
https://doi.org/10.1002/art.33376
[9]
Silva-Ramirez, B., Cerda-Flores, R.M., Rubio-Pérez, N., Vargas-Alarcón, G., Pérez-Hérnándes, N., et al. (2010) Association of HLA DRB1 Alleles with Juvenile Rheumatoid Arthritis in Mexicans. Clinical and Experimental Rheumatology, 28, 124-127.
[10]
Petty, R.E., Laxer, R., Lindsley, C., Wedderburn, L., Fuhlbrigge, R. and Mellins, E. (2021) Textbook of Pediatric Rheumatology. 8th Edition, Elsevier, Philadelphia.
[11]
Glass, D.N. and Gianini, E.H. (1999) Juvenile Rheumatoid Arthritis as a Complex Genetic Trait. Arthritis & Rheumatism, 42, 2261-2268.
https://doi.org/10.1002/1529-0131(199911)42:11<2261::AID-ANR1>3.0.CO;2-P
[12]
Prahalad, S. and Glass, D.N. (2008) A Comprehensive Review of the Genetics of Juvenile Idiopathic Arthritis. Pediatric Rheumatology, 6, Article No. 11.
https://doi.org/10.1186/1546-0096-6-11
[13]
Rachelefsky, G.S., Teresaki, P.I. and Katz, R. (1974) Increased Prevalence of B27 in Juvenile Rheumatoid Arthritis. The New England Journal of Medicine, 290, 892-893. https://doi.org/10.1056/NEJM197404182901608
[14]
Farivar, S., Shiari, R. and Hadi, E. (2011) Genetic Susceptibility to Juvenile Idiopathic Arthritis in Iranian Children. Archives of Medical Research, 41, 301-304.
https://doi.org/10.1016/j.arcmed.2011.05.004
[15]
Thomson, W., Barrett, J.H., Donn, R., Pepper, L., Kennedy, L.J., et al. (2002) Juvenile Idiopathic Arthritis Classified by the ILAR Criteria: HLA associations in UK Patients. Rheumatology, 41, 1183-1189.
https://doi.org/10.1093/rheumatology/41.10.1183
[16]
De Silvestri, A., Capittini, C., Poddighe, D., Marseglia, G.L., Mascaretti, L., Bevilacqua, E., et al. (2017) HLA-DRB1 Alleles and Juvenile Idiopathic Arthritis: Diagnostic Clues Emerging from a Meta-Analysis. Autoimmunity Reviews, 16, 1230-1236.
https://doi.org/10.1016/j.autrev.2017.10.007
[17]
Hinks, A., Bowes, J., Cobb, J., Anisworthh, H.C., Marion, M.C., Comeau, M.E., et al. (2017) Fine-Mapping the MHC Locus in Juvenile Idiopathic Arthritis (JIA) Reveals Genetic Heterogenicity Corresponding to Distinct Adult Inflammatory Arthritic Disease. Annals of the Rheumatic Diseases, 76, 765-772.
https://doi.org/10.1136/annrheumdis-2016-210025
[18]
Rahman, S.A., Islam, M.I., Hossain, M. and Talukder, M.K. (2008) Clinical Presentation of Juvenile Idiopathic Arthritis in Bangladesh: Experience from a Tertiary Hospital. International Journal of Rheumatic Diseases, 11, 50-54.
https://doi.org/10.1111/j.1756-185X.2008.00330.x
[19]
Rahman, S.A., Islam, M.I. and Talukder, M.K. (2013) Clinical Aspects of Juvenile Idiopathic Arthritis: Extended Experience from Bangladesh. American Journal of Clinical and Experimental Medicine, 1, 20-23.
https://doi.org/10.11648/j.ajcem.20130101.14
[20]
Rumana, R., Das, S., Islam, M.I. and Rahman, S. (2020) Assessment of Anaemia in Children with Juvenile Idiopathic Arthritis and Its Relationship with Disease Activity and Disease Duration. European Journal of Pharmaceutical and Medical Research, 7, 570-574.
[21]
Seth, V., Kabra, S.K., Semwal, O.P. and Jain, Y. (1996) Clinico-Immunological Profile in Juvenile Rheumatoid Arthritis—An Indian Experience. The Indian Journal of Pediatrics, 63, 293-300. https://doi.org/10.1007/BF02751521
[22]
Hegde, A., Acharya, S., Singh, K. and Kovilapu, U.B. (2020) Clinical Profile of Juvenile Idiopathic Arthritis from a Tertiary Care Hospital in Northern India. Indian Journal of Rheumatology, 15, 310-316.
[23]
Shiff, N.J., Oen, K., Kroeker, K. and Lix, L.M. (2019) Trends in Population-Based Incidence and Prevalence of Juvenile Idiopathic Arthritis in Manitoba, Canada. Arthritis Care & Research, 71, 413-418.
[24]
Islam, M.I., Laila, K. and Rahman, S.A. (2019) Pattern and Frequency of Anti-Nuclear Antibody Positivity in Paediatric Rheumatic Diseases. Bangladesh Journal of Child Health, 43, 21-26. https://doi.org/10.3329/bjch.v43i1.41212
[25]
Aggarwal, A. and Misra, R. (1994) Juvenile Chronic Arthritis in India: Is It Different from that Seen in Western Countries? Rheumatology International, 14, 53-56.
https://doi.org/10.1007/BF00300247
[26]
Shih, Y.-J., Yang, Y.-H., Lin, C.-Y., Chang, C.-L. and Chiang, B.-L. (2019) Enthesitis-Related Arthritis Is the Most Common Category of Juvenile Idiopathic Arthritis in Taiwan and Presents Persistent Active Disease. Paediatric Rheumatology, 17, Article No. 58. https://doi.org/10.1186/s12969-019-0363-0
[27]
Stanevicha, V., Eglite, J., Zavadska, D., Sochnevs, A., Lazareva, A., Guseinova, D., Shantere, R. and Gardovska, D. (2010) HLA B27 Allele Types in Homogeneous Groups of Juvenile Idiopathic Arthritis Patients in Latvia. Pediatric Rheumatology, 14, Article No. 26. https://doi.org/10.1186/1546-0096-8-26
[28]
Berntson, L., Damgård, M., Andersson-Gäre, B., et al. (2008) HLA-B27 Predicts a More Extended Disease with Increasing Age at Onset in Boys with Juvenile Idiopathic Arthritis. Journal of Rheumatology, 35, 2055-2061.
[29]
Islam, M.S., Sonia, S.P., Haque, M., Laila, K., et al. (2022) Disease Activity States of Juvenile Idiopathic Arthritis in a Referral Centre in Bangladesh. Bangladesh Medical Research Council Bulletin, 48, 41-47. https://doi.org/10.3329/bmrcb.v48i1.60659
[30]
Laila, K., Haque, M., Islam, M., Islam, M.I., Talukder, M.K., et al. (2016) Impact of Juvenile Idiopathic Arthritis on School Attendance and Performance. American Journal of Clinical and Experimental Medicine, 4, 185-190.
https://doi.org/10.11648/j.ajcem.20160406.15
[31]
Bochukova, E.G., Huang, N., Keogh, J., Henning, E., Purmann, C., Blaszczyk, K., et al. (2009) Large, Rare Chromosomal Deletions Associated with Severe Early-Onset Obesity. Nature, 463, 666-670. https://doi.org/10.1038/nature08689
[32]
Imielinski, M., Baldassano, R.N., Griffiths, A., Russell, R.K., Annese, V., Dubinsky, M., et al. Common Variants at Five New Loci Associated with Early-Onset Inflammatory Bowel Disease. Nature Genetics, 41, 1335-1340.
https://doi.org/10.1038/ng.489
[33]
Erlich, H., Valdes, A.M., Noble, J., Carlson, J.A., Varney, M., Concannon, P., et al. (2008) HLA DR-DQ Haplotypes and Genotypes and Type 1 Diabetes Risk: Analysis of the Type 1 Diabetes Genetics Consortium Families. Diabetes, 57, 1084-1092.
https://doi.org/10.2337/db07-1331
[34]
Gbadegesin, R.A., Adeyemo, A., Webb, N.J.A., Greenbaum, L.A., Abeyagunawardena, A., Thalgahagoda, S., et al. (2015) HLA-DQA1 and PLCG2 Are Candidate Risk Loci for Childhood-Onset Steroid-Sensitive Nephrotic Syndrome. JASN, 26, 1701-1710. https://doi.org/10.1681/ASN.2014030247