Focus on the spondyloarthritides. Can earlier diagnosis change the course of the disease?

The spondyloarthritides (or spondyloarthropathies) (SPAs) are chronic, inflammatory, rheumatic diseases of unknown origin, which share certain clinical, epidemiological, and genetic characteristics. They include ankylosing spondylitis, reactive arthritis (also known as the Reiter Syndrome), psoriatic arthritis, enteropathic spondyloarthropathy (ulcerative colitis, Crohn’s disease), undifferentiated spondyloarthritis, juvenile spondyloarthritis, and formes frustes such as acute anterior uveitis, spondyloarthritic carditis, and balanitis circinata. In the past, the SPAs were considered variants of rheumatoid arthritis, but it is now clear that they differ from the latter disease in terms of the pattern of articular and extra-articular involvement, their lack of association with seropositivity for rheumatoid factor, and their strong association with sacro-iliac joint bacino= pelvis sacro-iliac joint sacro-iliac joint sacro-iliac joint sacro-iliac joint sacro-iliac joint the class I human leukocyte antigen B27. sacro-iliac joint bacino= pelvis sacro-iliac joint sacro-iliac joint sacro-iliac joint sacro-iliac joint sacro-iliac joint Their general characteristics are axial involvement; enthesitis; peripheral arthritis involving the lower limbs, which is usually asymmetric; dactylitis; extra-articular manifestations involving the skin, eyes, bowel, and genitals. The musculoskeletal manifestations of the SPAs are due to inflammation at the level of the entheses. It is important to distinguish between the numerous clinical SPA variants based on analysis of symptoms, laboratory tests, and instrumental studies. Thanks to a greater understanding of the pathogenesis of the SPAs and the widespread availability of highly sensitive imaging modalities for their diagnosis, it is now possible to identify these diseases early and modify their course with effective therapy. This approach offers benefits to patients in terms of reduced morbidity and mortality and improved quality of life.

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Juvenile Spondyloarthritis: What More Do We Know About HLA-B27, Enthesitis, and New Bone Formation?

Frontiers in Medicine ◽

10.3389/fmed.2021.666772 ◽

2021 ◽

Vol 8 ◽

Author(s):

Shi Huan Tay ◽

Joo Guan Yeo ◽

Jing Yao Leong ◽

Salvatore Albani ◽

Thaschawee Arkachaisri

Keyword(s):

Bone Formation ◽

Treatment Options ◽

Strong Association ◽

Human Leukocyte ◽

Childhood And Adolescence ◽

Hla B27 ◽

New Bone Formation ◽

Leukocyte Antigen ◽

Immune Mediated ◽

Juvenile Spondyloarthritis

Juvenile spondyloarthritis (JSpA) refers to a diverse spectrum of immune-mediated inflammatory arthritides whose onset occurs in late childhood and adolescence. Like its adult counterpart, JSpA is typified by a strong association with human leukocyte antigen-B27 (HLA-B27) and potential axial involvement, while lacking rheumatoid factor (RF) and distinguishing autoantibodies. A characteristic manifestation of JSpA is enthesitis (inflammation of insertion sites of tendons, ligaments, joint capsules or fascia to bone), which is commonly accompanied by bone resorption and new bone formation at affected sites. In this Review, advances in the role of HLA-B27, enthesitis and its associated osteoproliferation in JSpA pathophysiology and treatment options will be discussed. A deeper appreciation of how these elements contribute to the JSpA disease mechanism will better inform diagnosis, prognosis and therapy, which in turn translates to an improved quality of life for patients.

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Spectrum of cutaneous adverse reactions to aromatic antiepileptic drugs and human leukocyte antigen genotypes in Thai patients and meta-analysis

The Pharmacogenomics Journal ◽

10.1038/s41397-021-00247-3 ◽

2021 ◽

Author(s):

Chonlaphat Sukasem ◽

Suthida Sririttha ◽

Chonlawat Chaichan ◽

Thapanat Nakkrut ◽

Patompong Satapornpong ◽

...

Keyword(s):

Human Leukocyte Antigen ◽

Antiepileptic Drugs ◽

Meta Analysis ◽

Strong Association ◽

Human Leukocyte ◽

Stevens Johnson Syndrome ◽

Thai Population ◽

Leukocyte Antigen ◽

Maculopapular Eruption ◽

Sequence Specific Oligonucleotide Probe

AbstractAromatic antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs) add up to the limited use of the AEDs in the treatment and prevention of seizures. Human leukocyte antigen-B (HLA-B) alleles have been linked to AEDs-induced cADRs. We investigated the association between cADRs (including Stevens–Johnson syndrome; SJS/toxic epidermal necrolysis; TEN, drug reaction with eosinophilia and systemic symptoms; DRESS, and Maculopapular eruption; MPE) caused by AEDs (phenytoin, carbamazepine, lamotrigine, phenobarbital and oxcarbazepine) and HLA-B alleles in Thai population. Through the case-control study, 166 patients with AEDs-induced cADRs, 426 AEDs-tolerant patients (AEDs-tolerant controls), and 470 healthy subjects (Thai population) were collected. The HLA genotypes were detected using the polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. We also performed a meta-analysis with these data and other populations. The carrier rate of HLA-B*15:02 was significantly different between AEDs-induced cADRs group and AEDs-tolerant group (Odds ratio; OR 4.28, 95% Confidence interval; CI 2.64–6.95, p < 0.001), AEDs-induced cADRs group and Thai population (OR 2.15, 95%CI 1.41–3.29, p < 0.001). In meta-analysis showed the strong association HLA-B*15:02 with AEDs-induced cADRs (OR 4.77, 95%CI 1.79–12.73, p < 0.001). Furthermore, HLA-B*15:02 was associated with SJS/TEN induced by AEDs (OR 10.28, 95%CI 6.50–16.28, p < 0.001) Phenytoin (OR 4.12, 95%CI 1.77–9.59, p = 0.001) and carbamazepine (OR 137.69, 95%CI 50.97–371.98, p < 0.001). This study demonstrated that genetic association for AEDs-induced cADRs was phenotype-specific. A strong association between HLA-B*15:02 and AEDs-induced SJS/TEN was demonstrated with an OR of 10.79 (95%CI 5.50–21.16, p < 0.001) when compared with AEDs-tolerant group. On the other hand, the carrier rates of HLA-B*08:01, HLA-B*13:01, and HLA-B*56:02 were significantly higher in the DRESS group compared with the AEDs-tolerant group (p = 0.029, 0.007, and 0.017, respectively). The HLA-B*15:02 allele may represent a risk factor for AEDs-induced cADRs.

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Shared HLA Class II in Six Autoimmune Diseases in Latin America: A Meta-Analysis

Autoimmune Diseases ◽

10.1155/2012/569728 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 8

Author(s):

Paola Cruz-Tapias ◽

Oscar M. Pérez-Fernández ◽

Adriana Rojas-Villarraga ◽

Alberto Rodríguez-Rodríguez ◽

María-Teresa Arango ◽

...

Keyword(s):

Risk Factor ◽

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Meta Analysis ◽

Human Leukocyte ◽

Class Ii ◽

Hla Class Ii ◽

Genetic Characteristics ◽

Latin Americans ◽

Leukocyte Antigen

The prevalence and genetic susceptibility of autoimmune diseases (ADs) may vary depending on latitudinal gradient and ethnicity. The aims of this study were to identify common human leukocyte antigen (HLA) class II alleles that contribute to susceptibility to six ADs in Latin Americans through a meta-analysis and to review additional clinical, immunological, and genetic characteristics of those ADs sharing HLA alleles. DRB1∗03:01 (OR: 4.04; 95%CI: 1.41–11.53) was found to be a risk factor for systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), and type 1 diabetes mellitus (T1D). DRB1∗04:05 (OR: 4.64; 95%CI: 2.14–10.05) influences autoimmune hepatitis (AIH), rheumatoid arthritis (RA), and T1D; DRB1∗04:01 (OR: 3.86; 95%CI: 2.32–6.42) is a susceptibility factor for RA and T1D. Opposite associations were found between multiple sclerosis (MS) and T1D. DQB1∗06:02 and DRB1∗15 alleles were risk factors for MS but protective factors for T1D. Likewise, DQB1∗06:03 allele was a risk factor for AIH but a protective one for T1D. Several common autoantibodies and clinical associations as well as additional shared genes have been reported in these ADs, which are reviewed herein. These results indicate that in Latin Americans ADs share major loci and immune characteristics.

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A strong association of human leukocyte antigen-associated Pol and Gag mutations with clinical parameters in HIV-1 subtype A/E infection

AIDS ◽

10.1097/qad.0000000000000969 ◽

2016 ◽

Vol 30 (5) ◽

pp. 681-689 ◽

Cited By ~ 11

Author(s):

Giang Van Tran ◽

Takayuki Chikata ◽

Jonathan M. Carlson ◽

Hayato Murakoshi ◽

Dung Hoai Nguyen ◽

...

Keyword(s):

Human Leukocyte Antigen ◽

Strong Association ◽

Human Leukocyte ◽

Clinical Parameters ◽

Leukocyte Antigen ◽

Subtype A ◽

Hiv 1

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GENETIC CHARACTERISTICS OF THE POPULATION LIVING IN THE TERRITORY OF THE REPUBLIC OF BASHKORTOSTAN

Russian Journal of Transplantology and Artificial Organs ◽

10.15825/1995-1191-2016-1-58-66 ◽

2016 ◽

Vol 18 (1) ◽

pp. 58-66 ◽

Cited By ~ 1

Author(s):

M. A. Loginova ◽

I. V. Paramonov ◽

V. N. Pavlov ◽

G. Sh. Safuanova

Keyword(s):

Haplotype Analysis ◽

Human Leukocyte ◽

The Other ◽

Hematopoietic Stem ◽

Genetic Characteristics ◽

Leukocyte Antigen ◽

Republic Of Bashkortostan ◽

The Russian Federation ◽

The Republic ◽

New Alleles

Sequence based typing was used to identify human leukocyte antigen (HLA)-A, -B, -C, -DRB1 alleles in 1,064 recruited volunteers in the Republic of Bashkortostan of the Russian Federation for unrelated hematopoietic stem cell registry. During the carried out research two new alleles were identified in the studied population; one was registered in the WHO Nomenclature Committee for Factors of the HLA System, the other one was submitted for registration. In this population 17 HLA-A, 29 – HLA-B, 13 – HLA-C, 13 – HLA-DRB1 groups of alleles were selected. Allele frequencies of more than 10% included HLA-A*02 (29.37%), 24 (12.92%), 01 (11.84%), 03 (11.61%), HLA-B*35 (11.51%), 07 (10.76%), HLA-C*07 (22.56%), 06 (15.51%), 04 (13.06%), 03 (10.43%), 12 (10.24%), HLA-DRB1*07 (17.25%), 15 (12.73%), 13 (11.98%), 01 (11.84%), 04 (11.61%). 711 HLA-A-B-C-DRB1 four-locus haplotypes were determined using the software Arlequin v.3.1. The most frequently observed four-locus haplotypes were A*02-B*13-C*06-DRB1*07, A*03-B*35-C*07-DRB1*15, A*02- B*07-C*07-DRB1*15 with frequencies of 2.89%, 2.18% and 1.93%, respectively. The distribution of alleles and haplotype analysis allowed comparing the populations of the Republic of Bashkortostan with the other Russian populations.

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Epidemiology of axial spondyloarthritis

10.1093/med/9780198734444.003.0002 ◽

2016 ◽

Author(s):

Lianne Gensler ◽

Michael Weisman ◽

Liron Caplan

Keyword(s):

External Validity ◽

Inflammatory Arthritis ◽

Axial Spondyloarthritis ◽

Strong Association ◽

Human Leukocyte ◽

Epidemiological Studies ◽

Hla B27 ◽

Sacroiliac Joints ◽

Leukocyte Antigen ◽

Inflammatory Bowel

Axial spondyloarthritis (axSpA) is an inflammatory arthritis of the sacroiliac joints and spine. The prototype is ankylosing spondylitis, the radiographic form of the disease; however, more recently, an earlier or less-differentiated presentation has been described termed non-radiographic axial spondyloarthritis (nr-axSpA). Extra-articular manifestations commonly include anterior uveitis, inflammatory bowel disease, and psoriasis. There is a strong association with the human leukocyte antigen B27 (HLA-B27) allele, and the prevalence of the disease tends to follow the frequency of the allele. Epidemiological studies in axSpA are relevant in the population studied and therefore have limited external validity. This chapter describes the epidemiology of axSpA.

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Narcolepsy as an Immune-Mediated Disease

Sleep Disorders ◽

10.1155/2014/792687 ◽

2014 ◽

Vol 2014 ◽

pp. 1-6 ◽

Cited By ~ 20

Author(s):

Alberto K. De la Herrán-Arita ◽

Fabio García-García

Keyword(s):

Influenza A ◽

Molecular Mimicry ◽

Strong Association ◽

Human Leukocyte ◽

Cell Receptor ◽

H1n1 Vaccine ◽

Leukocyte Antigen ◽

Immune Mediated ◽

Influenza A H1n1 ◽

2009 H1n1

Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness, cataplexy, hypnagonic hallucinations, sleep paralysis, and disturbed nocturnal sleep patterns. This disease is secondary to the specific loss of hypothalamic hypocretin (orexin)-producing neurons in the lateral hypothalamus. An autoimmune basis for the disease has long been suspected based on its strong association with the genetic marker DQB1*06:02, and current studies greatly support this hypothesis. Narcolepsy with hypocretin deficiency is associated with human leukocyte antigen (HLA) and T cell receptor (TCR) polymorphisms, suggesting that an autoimmune process targets a peptide unique to hypocretin-producing neurons via specific HLA-peptide-TCR interactions. This concept has gained a lot of notoriety after the increase of childhood narcolepsy in 2010 following the 2009 H1N1 pandemic (pH1N1) in China and vaccination with Pandemrix, an adjuvanted H1N1 vaccine that was used in Scandinavia. The surge of narcolepsy cases subsequent to influenza A H1N1 infection and H1N1 vaccination suggests that processes such as molecular mimicry or bystander activation might be crucial for disease development.

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Association of human leukocyte antigen variants and allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: A meta-analysis

American Journal of Health-System Pharmacy ◽

10.2146/ajhp160243 ◽

2017 ◽

Vol 74 (9) ◽

pp. e183-e192 ◽

Cited By ~ 4

Author(s):

Xingang Li ◽

Zhigang Zhao ◽

Shu-Sen Sun

Keyword(s):

Human Leukocyte Antigen ◽

Toxic Epidermal Necrolysis ◽

Fixed Effects ◽

Meta Analysis ◽

Strong Association ◽

Human Leukocyte ◽

Stevens Johnson Syndrome ◽

Leukocyte Antigen ◽

Johnson Syndrome ◽

Population Controls

Abstract Purpose The association between human leukocyte antigen (HLA) variants and allopurinol-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) was evaluated through a pooled analysis of published studies. Methods A comprehensive search was performed in multiple databases, including PubMed, MEDLINE, ISI Web of Knowledge, EMBASE, Cochrane Register of Controlled Trials, and Science Direct. Studies investigating the association between HLA alleles with allopurinol-induced SJS or TEN were retrieved, and the data were independently extracted. The overall odds ratios (ORs) with corresponding 95% confidence intervals were calculated to determine the association between the presence of HLA variant in at least one allele and allopurinol-induced SJS or TEN. To test the robustness of the meta-analysis results, a sensitivity analysis was performed by removing each study one at a time and calculating the pooled ORs of the remaining studies. The fixed-effects and random-effects models were used to pool the collected data. Results A total of 4 studies with 81 allopurinol-induced SJS or TEN cases and matched controls (allopurinol-tolerant patients) or population controls (general population) were identified. SJS and TEN were found to be significantly associated with HLA-A*33:03 and HLA-C*03:02 alleles in both groups of studies with matched controls and population controls. All of the pooled ORs were not significantly affected by the remaining studies and different modeling methods, indicating robust results. Conclusion A strong association was found between HLA-A*33:03 and HLA-C*03:02 alleles and allopurinol-induced SJS or TEN, especially in an Asian population.

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