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HLA-B27 polymorphism in the Malays

Dhaliwal JS, Too CL, Lisut M, Lee YY, Murad S

Tissue Antigens, 2003 Oct;62(4):330-2.
PMID: 12974801

The frequency of HLA-B27 and its subtypes was determined in 878 Malay subjects. Thirty-five of the subjects typed for HLA-A, -B and -DR were found to be positive for HLA-B27. The frequency of this allele in the Malay population was found to be 3.99%. The subtypes observed and their frequencies are: HLA-B*2704 (19.4%), HLA-B*2705 (5.6%), HLA-B*2706 (72.2%) and HLA-B*2707 (2.8%).

Matched MeSH terms: HLA-B27 Antigen/blood; HLA-B27 Antigen/genetics*
A novel HLA-B*27 allele, B*27:138, identified by sequence-based typing

Koay BT, Norfarhana KF, Norhafizi MY, Lee YY, Dhaliwal JS

Tissue Antigens, 2015 Aug;86(2):143-4.
PMID: 26105122 DOI: 10.1111/tan.12599

Ankylosing spondylitis (AS) is a chronic inflammatory disorder with predilection for the axial skeleton, leading to progressive restricted mobility and deformity of the spine. The fundamental mechanism involves autoimmunity orchestrated by T cells. Similar to other rheumatic diseases, the complex interplay of cytokines such as tumour necrosis factor alpha, interleukin-6 (IL 6) and interleukin-10 (IL 10) has been implicated in the pathogenesis of the disease. Despite extensive research over the past decades, the treatment options for AS, are limited. Non steroidal antiinflammatory drugs are the first line of therapy, whereas anti TNF drugs are administered for refractory cases which fail to respond to the treatment. There have been conflicting views on the correlation of IL 6 with disease activity in AS. As such, the debate on the role of anti IL6 in AS is still ongoing. Anti IL 6 such as tocilizumab and siltuximab have proven efficacy based on the large randomized controlled trials. The Food and Drug Administration (FDA) has approved these drugs for treating rheumatoid arthritis and systemic juvenile idiopathic arthritis. Researchers have adventurously experimented anti IL 6 therapy in AS but the conclusions made were not consolidated into international guidelines or consensus statement for clinical practice. In the present review, we explore the role of anti IL6 in the treatment of AS based on the cumulative evidence over recent years.

Matched MeSH terms: HLA-B27 Antigen/genetics*
Spondyloarthropathies in eastern Asia

Feltkamp TE, Mardjuadi A, Huang F, Chou CT

Curr Opin Rheumatol, 2001 Jul;13(4):285-90.
PMID: 11555729

The association between HLA-B27 and the spondyloarthropathies (SpAs) is so strong that it is supposed that the HLA-B27 molecule plays a pathogenetic role. In whites and Indonesians, the frequency of HLA-B27 is about 10%; in Chinese it is about 8%; and in Japanese it is only about 1%. The prevalence of SpA in the Chinese is at least 0.2%, but in native Indonesians, Philippinos, and Malaysians, SpA is rarely seen. Twenty-three subtypes (B*2701-B*2723) have been distinguished. These subtypes are not equally distributed over the world. In most countries the distribution of the subtypes among HLA-B27 SpA patients is the same as that among the normal HLA-B27-positive population. In China, the subtype B*2704 is frequent and the prevalence of SpA is high. Native Indonesians, however, mostly have subtype B*2706, and SpA is rarely seen in this population. It was shown that B*2706, probably like B*2709 in Sardinia, is not associated with SpA. The difference between the SpA-associated and non-SpA-associated subtypes is limited to only two amino acid residues (114 and 116) at the bottom of the peptide-binding groove of HLA-B27. This small difference between health and disease rewards studies for different peptide-binding capacities and may help us characterize the peptides that are involved in the pathogenesis of SpA. The differences in disease associations in these countries also have clinical implications. In Southeast Asia, HLA-B27 typing without subtyping has less clinical usefulness than in parts of the world where B*2706 is rarely seen. When native Indonesians, Malaysians, or Philippinos are suspected of having ankylosing spondylitis or a related SpA, it is worth asking if they had white or Chinese ancestors. If native HLA-B27-positive Indonesians (with subtypes other than B*2706) develop SpA, the clinical features are not different from those in other parts of the world. In the Chinese population on the mainland and in Taiwan, juvenile SpA is frequently seen. The onset is often a peripheral arthritis or enthesitis.

Matched MeSH terms: HLA-B27 Antigen/genetics
Pattern of psoriatic arthritis in an Asian population (Malaysia)

Veerapen KK

APLAR Journal of Rheumatology, 2007;10(4):287-294.
DOI: 10.1111/j.1479-8077.2007.00308.x

Objective: To profile the pattern of psoriatic arthritis (PsA) and its relationship to disease duration. Methods: Forty-six consecutive patients with PsA were entered into a cross-sectional study. Demographic data, disease duration and disability were recorded. Joint involvement was documented at 6 months from onset and at presentation. X-rays of the sacroiliac (SI) joints, thoracolumbar spine, and hands were taken. HLA B27 typing was done. Results: The male: Female ratio was 2.3: 1, mean age at onset of arthritis was 35.8 years and mean duration of PsA was 4.2 years. Oligoarticular involvement predominated (63%) at onset. Progression from oligoarthritis to polyarthritis occurred largely in the second year; 65.2% reported asymmetrical disease at onset while 50% had asymmetrical disease when disease duration was >.1 year. The frequency of involvement at onset was as follows: Sausage toes, metatarsophalangeals (MTPs) and interphalangeals (IPs) in 50% (each), proximal interphelangeals (PIPs) in 47.8%, sausage fingers 34.7% and knees 30%. With mean duration of 4.2 years it was: Sausage toe 71.1%, IP 69.5%, PIP and MTP 63%, knees 60.8%, distal interphalangeals (DIPs) 54.3%, sausage finger 52.1%, wrist 47.8%, followed by neck and back pain. Disability related to lower limb functions predominated and occurred early. Forty-one percent had radiological sacroiliatis/spondylitis and 46% had erosive arthritis in the hands; 10.2% were HLA B27 positive. Conclusion: PsA was progressive, starting predominantly as an asymmetrical oligoarthritis and becoming largely polyarticular within 2 years from onset. Lower limb disability was evident early and erosive changes in hand X-rays were seen in more than half the patients after 1 year. © 2007 Asia Pacific League of Associations for Rheumatology.

Matched MeSH terms: HLA-B27 Antigen
Fulltext Exploring sub-optimal response to tumour necrosis factor inhibitors in axial spondyloarthritis

Yahya F, Gaffney K, Sengupta R

Rheumatol Adv Pract, 2019;3(1):rkz012.
PMID: 31432000 DOI: 10.1093/rap/rkz012

Objectives: The aim was to define sub-optimal response to TNF inhibitors (TNFi), compare long-term drug survival rates and identify predictors of sub-optimal response in axial spondyloarthritis (axSpA) patients in a UK cohort.
Methods: All axSpA patients attending two centres who commenced TNFi between 2002 and 2016 were included. Routinely recorded patient data were reviewed retrospectively. Patients with paired BASDAI at baseline, 3 and/or 6 months were included for analysis. Sub-optimal response was defined as achieving a ≥ 2-point reduction in BASDAI but not BASDAI50, post-treatment BASDAI remaining at ≥4, and in the opinion of the treating physician these patients demonstrated a meaningful clinical response.
Results: Four hundred and ninety-nine patients were included: 82 (16.4%) patients were classified as having a sub-optimal response; 64 (78%) males, 78 (95.1%) AS and 55/67 (82.1%) HLA-B27 positive. Results are reported as the mean (s.d.). Time to diagnosis was 10 (8.6) years, age at diagnosis was 37 (11.7) years, and age at initiating index TNFi was 48 (11.1) years. Individual index TNFi were Humira (adalimumab, n = 41, 50%), Enbrel (etanercept, n = 27, 32.9%), Remicade (infliximab, n = 5, 6.1%), Simponi (golimumab, n = 3, 3.7%) and Cimzia (certolizumab pegol, n = 6, 7.3%). The rate of attrition was greater among sub-optimal responders at 2 and 5 years (P

Matched MeSH terms: HLA-B27 Antigen
Tumour necrosis factor inhibitor survival and predictors of response in axial spondyloarthritis-findings from a United Kingdom cohort

Yahya F, Gaffney K, Hamilton L, Lonsdale E, Leeder J, Brooksby A, et al.

Rheumatology (Oxford), 2018 Apr 01;57(4):619-624.
PMID: 29272541 DOI: 10.1093/rheumatology/kex457

Objectives: To analyse long-term survival and efficacy of TNFi, reasons for switching or discontinuing, baseline predictors of response and remission in axial spondyloarthritis (axSpA) patients in a UK cohort.
Methods: All patients with a physician-verified diagnosis of axSpA attending two specialist centres who fulfilled the eligibility criteria for TNFi were included. Routinely recorded patient data were reviewed retrospectively. Initial TNFi was recorded as the index drug.
Results: Six hundred and fifty-one patients (94% AS) were included; adalimumab (n = 332), etanercept (n = 205), infliximab (n = 51), golimumab (n = 40) and certolizumab pegol (n = 23) were index TNFi. The mean (s.d.) duration from symptom onset to time of diagnosis was 8.6 (8.7) years and mean (s.d.) duration from diagnosis to TNFi initiation was 12.6 (11.5) years. A total of 224 (34.4%) stopped index TNFi, and 105/224 switched to a second TNFi. Median drug survival for index and second TNFi were 10.2 years (95% CI: 8.8, 11.6 years) and 5.5 years (95% CI: 2.7, 8.3 years), respectively (P < 0.05). Survival rates were not influenced by choice of TNFi. HLA-B27 predicted BASDAI50 and/or two or more point reduction within 6 months and long-term drug survival (P < 0.05). Low disease activity was predicted by non-smoking and low baseline BASDAI (P < 0.05).
Conclusion: We have observed good TNFi survival rates in axSpA patients treated in a real-life setting. This is best for first TNFi and not influenced by drug choice.

Matched MeSH terms: HLA-B27 Antigen
HLA-A, -B, -C, -DRB1 and -DQB1 alleles and haplotypes in 951 Southeast Asia Malays from Peninsular Malaysia

Tan LK, Mohd-Farid B, Salsabil S, Heselynn H, Wahinuddin S, Lau IS, et al.

Hum Immunol, 2016 Oct;77(10):818-819.
PMID: 27370684 DOI: 10.1016/j.humimm.2016.06.022

A total of 951 Southeast Asia Malays from Peninsular Malaysia were genotyped for HLA-A, -B, -C -DRB1, and -DQB1 loci using polymerase chain reaction sequence-specific oligonucleotide probe hybridization methods. In this report, there were significant deviation from Hardy-Weinberg proportions for the HLA-A (p<0.0001), -B (p<0.0001), -DRB1 (p<0.0001) and -DQB1 (p<0.01) loci. Minor deviations from HWEP were detected for HLA-C (p=0.01). This genotype data was available in Allele Frequencies Network Database (AFND) Gonzalez-Galarza et al. (2015).

Matched MeSH terms: HLA-B27 Antigen/genetics*