Presence Of HLA-B Research Articles

Association of KIR2DL5, KIR2DS5, and KIR2DS1 allelic variation and atopic dermatitis

Natural killer cells (NK) have been associated with the pathophysiology of atopic dermatitis (AD). NK function is regulated by killer cell Ig-like receptor family (KIR) receptors that interact with HLA ligands. The study goal was to focus on allelic variation in genes KIR2DL5, KIR2DS5, and KIR2DS1 with respect to AD. This was a case–control study of individuals with (n = 313) and without (n = 176) AD. Associations were estimated using logistic regression. The prevalence of KIR2DL5 was 52.5% (95% CI 48.0,57.0), KIR2DS5 was 33.0% (28.8,37.3), and KIR2DS1 was 33.6% (29.4,38.0). The presence of the KIR2DL5*001:01 increased the odds of having AD by about 86% (odds ratio (OR): 1.86(1.23,2.82) p = 0.003). The risk for individuals homozygous for KIR2DL5*001:01 was even greater (OR: 2.16 (95% CI 1.31,3.53) p = 0.0023). The odds of having AD with KIR2DL5*001:01 was similar in Whites and Blacks. Allelic variation in KIR2DS5 and KIR2DS1 was not associated with AD. There is no known HLA binding ligand for KIR2DL5. The effect of KIR2DL5*001:01 increased in the presence of HLA-B*-21TT leader sequence (2.46(1.37,4.41) p = 0.0025) and the HLA-C2 ligand (2.07 (1.37,4.41, p = 0.000002). Our study shows an independent association of the KIR2DL5*001:01 with AD and is the first study to associate AD with KIR allelic variation.

Next-generation sequencing-based HLA typing reveals the association of HLA-B*46:01:01 and HLA-DRB1*09:01:02 alleles with carbamazepine-induced hypersensitivity reactions in Vietnamese patients with epilepsy

Several studies have reported an association between certain human leukocyte antigen (HLA) alleles and carbamazepine (CBZ)-induced hypersensitivity reactions in patients with epilepsy. Here, the relationship between the clinical spectrum and the HLA allele profiles in patients with CBZ-induced hypersensitivity reactions was investigated using next-generation sequence (NGS) data obtained from 65 Vietnamese patients with epilepsy, including 33 with CBZ-tolerance and 32 patients with CBZ-hypersensitivity, in which only 8 with severe cutaneous adverse drug reactions and 24 were mild-hypersensitive patients. Three loci of HLA class I (HLA-A, -B, and -C) and two loci of HLA class II (HLA-DQA1 and -DRB1) were included in our analysis. We observed a higher prevalence of three alleles, HLA-B*46:01:01, HLA-DQA1*03:02:01, and HLA-DRB1*09:01:02, in the CBZ hypersensitivity group compared to that in the CBZ tolerant group. Notably, all hypersensitive patients with HLA-DQA1*03:02:01 also harbored HLA-DRB1*09:01:02. We also used molecular modeling to gain mechanistic insight into the interactions of HLA-B*46:01 and HLA-DRB1*09:01 with CBZ. Our findings proposed the direct interaction of CBZ with peptide-binding pockets of these HLA proteins. The sensitivity and specificity of HLA-B*46:01:01 in considering with the appearance of HLA-DRB1*09:01:02 were 46.88% and 84.85%, respectively. Our data suggest that the presence of HLA-B*46:01:01/HLA-DRB1*09:01:02 is a potential marker of CBZ-induced hypersensitivity reactions in Vietnamese patients.

P062 Chromoendoscopy With Magnification Colonoscopy: Analysis of Mucosa of Colon And Ileum In Patients With Gastrointestinal Symptoms Without IBD.

Digital chromoendoscopy (Narrow Band Imaging By Olympus) or BLI (Blue Light Imaging By Fujifilm), with the magnification endoscope, allows a detailed evaluation of the mucosal surface and its vascular network, which facilitates the diagnosis and monitoring of early lesions. This technique has demonstrated a better detection, which allows optical diagnosis during a colonoscopy examination. Patients with SpA with nonspecific gastrointestinal symptoms, subclinical intestinal inflammation are defined as endoscopic and histologically. The aim was to detect early structural inflammatory changes by chromoendoscopy and magnification colonoscopy in colonic/ileum digestive mucosa, and establish its association with clinical variables in SpA and gastrointestinal symptoms. Study approved by Institutional Ethics Committee, code HMC 2017-023. Clinical evaluation by rheumatologist in SpA patients (ASAS/criteria), fecal calprotectin levels, and HLA-B*27 were evaluated. In patients with ≥2 gastrointestinal symptoms, clinical evaluation by gastroenterologist, digital chromoendoscopy (NBI) or (BLI), magnification colonoscopy, and histological analysis were performed. The association between clinical and colonoscopy variables were established using the Chi-square or Fisher's exact test. In total, 62 SpA patients were included, with mean age of 45.1 ± 11.3 years, axial SpA (77.4%) peripheral SpA (12.9%), biological treatment (69.4%), ASDAS-CRP>2,1 (67.7%), presence of HLA-B*27 (41.9%). Patients with ≥2 gastrointestinal symptoms were found in 67.7%. The most important symptoms were abdominal pain (66.1%), abdominal distension (64.5%), and food intolerance (59.7%). 22.6% of patients showed high level of calprotectin. In those patients with gastrointestinal symptoms, chromoendoscopy and magnification colonoscopy were performed. The mean age of those patients was 45.4 ± 10.5, 57.6% were male, BMI>25 in 69.7%, presence of HLA-B*27 in 39.4%, 33.3% were former smokers, axial SpA in 84.8% and ASDAS-CRP>21 in 78.8%. In total, 27.27% of the patients presented high levels of calprotectin, of which 66.0% had more than two gastrointestinal symptoms (p = 0.015). 77.8% presented alterations in ileal mucosa (p=0.060). The most frequent alteration was the loss of vascular pattern (p = 0.002). By histological analysis, 5 patients had acute inflammation in the ileum, of which 4 had increased levels of fecal calprotectin (p = 0.013). 30.8% of patients positive for HLAB*27:05:02 had ulcers in ileum (p = 0.017) and 61.5% had chronic inflammatory patterns (p=0.020). Chromoendoscopy provided an enhanced, detailed contrast of the gastrointestinal mucosa surface, mainly in the loss of vascular pattern in ileum. The active search for symptoms, signs, and biomarkers of gastrointestinal involvement in addition to an objective endoscopic and histological evaluation may offer new perspectives at the evaluation of SpA patients and may provide guidance for specific clinical and therapeutic management.

Garcinia cambogia, Either Alone or in Combination With Green Tea, Causes Moderate to Severe Liver Injury

Garcinia cambogia, either alone or with green tea, is commonly promoted for weight loss. Sporadic cases of liver failure from G cambogia have been reported, but its role in liver injury is controversial.Among 1418 patients enrolled in the Drug-Induced Liver Injury Network (DILIN) from 2004 to 2018, we identified 22 cases (adjudicated with high confidence) of liver injury from G cambogia either alone (n = 5) or in combination with green tea (n = 16) or Ashwagandha (n = 1). Control groups consisted of 57 patients with liver injury from herbal and dietary supplements (HDS) containing green tea without G cambogia and 103 patients from other HDS.Patients who took G cambogia were between 17 and 54 years, with liver injury arising 13-223 days (median = 51) after the start. One patient died, one required liver transplantation, and 91% were hospitalized. The liver injury was hepatocellular with jaundice. Although the peak values of aminotransferases were significantly higher (2001 ± 1386 U/L) in G cambogia group (P < .018), the median time for improvement in total bilirubin was significantly lower compared with the control groups (10 vs 17 and 13 days; P = .03). The presence of HLA-B∗35:01 allele was significantly higher in the G cambogia containing HDS (55%) compared with patients because of other HDS (19%) (P = .002) and those with acute liver injury from conventional drugs (12%) (P = 2.55 × 10-6).The liver injury caused by G cambogia and green tea is clinically indistinguishable. The possible association with HLA-B∗35:01 allele suggests an immune-mediated mechanism of injury.gov number: NCT00345930.

Influence of HLA-B*5701 on 20 year survival rate among patients living with HIV.

BackgroundThe life expectancy of people living with HIV (PLWH) remains shorter than that of the general population, despite significant improvement in the recent years. Mortality in HIV-infected individuals may be associated with a higher viral load at of diagnosis, a lower CD4 count, or clinical variables such as sex or route of transmission. This article investigated the role of the HLA-B*5701 varian on mortality among PLWH.MethodsMaterial for the analysis consist of the data of 2,393 patients for whom the HLA-B*57 variant was known. Those patients were followed under the care of the Infectious Diseases Hospital in Warsaw (n = 1555) and the Clinic of Acquired Immunodeficiency of the Pomeranian Medical University in Szczecin (n = 838). Factors such as age, gender, date of HIV diagnosis, route of transmission, date of death, baseline HIV viral load and baseline CD4 counts, were collected, and end-point cross-sectional analyses were marked at 60, 120, 180 and 240 month of observation.ResultsHLA-B*5701 allele was found in 133 (5.5%) analyzed cases. Median age was notably higher for HLA-B*5701 positive patients [32.7 (28.3–41.3) vs. 31.6 (26.8–38.3)years p = 0.02]. HLA-B*5701 was associated with lower baseline viral load [4.21 (3.5–4.8) vs. 4.79 (4.2–5.3)log copies/ml p<0.001] and higher CD4count [448 (294.5–662) vs. 352 (176–514) cells/μl p<0.001]. There were no association between HLA-B*5701 and survival for any given end-point. Higher mortality was associated to male gender, intravenous drug users, lower CD4 count at baseline and higher baseline viral load.ConclusionsIn our study, the presence of HLA-B*5701 allel was not associated with mortality rate of HIV infected patients, irrespective of being associated with both higher baseline CD4 + cell count and lower baseline HIV viral load.

Prevalence of human leukocyte antigen HLA-B*57:01 in individuals with HIV in West and Central Africa

BackgroundThe presence of the human leukocyte antigen HLA-B*57:01 is associated with the development of a hypersensitivity reaction to abacavir (ABC). Limited data exist on HLA-B*57:01 prevalence in individuals with HIV-1 in Africa. This study aimed to estimate HLA-B*57:01 prevalence in individuals with HIV-1 in West and Central Africa.MethodsA cross-sectional study was conducted in four countries in West and central Africa (Burkina-Faso, Côte d’Ivoire, Gabon, and Togo) from January 2016 to February 2020 to determine the status of HLA-B*57:01 in adults with HIV-1. The presence of HLA-B*57:01 was determined by using Single Specific Primer-Polymerase Chain Reaction (SSP-PCR) in blood samples. Prevalence rates were stratified based on country.ResultsA total of 4016 (69.8% women) individuals with HIV were enrolled. Their median age was 45, and the interquartile range was 38–52. We included 500 (12.4%) patients in Burkina-Faso, 1453 (36.2%) in Côte d’Ivoire, 951 (23.7%) in Gabon, and 1112 (27.7%) in Togo. The overall HLA-B*57:01 prevalence was 0.1% [95% CI: 0.0–0.2%]. The prevalence of HLA-B*57:01 was similar according to the four countries. Only one case was reported in each country except Togo, with no cases.ConclusionsHLA-B*57:01 prevalence is low in individuals with HIV in West and central Africa, and there is no difference among countries. This study does not confirm the utility of HLA-B*57:01 allele testing for abacavir use in this region.

The presence of both HLA-DRB1*04:01 and HLA-B*15:01 increases the susceptibility to cranial and extracranial giant cell arteritis.

To determine if patients with the predominant extracranial large-vessel-vasculitis (LVV) pattern of giant cell arteritis (GCA) have a distinctive HLA-B association, different from that reported in biopsy-proven cranial GCA patients. In a further step we assessed if the combination of HLA-B and HLA-DRB1 alleles confers an increased risk for GCA susceptibility, either for the cranial and extracranial LVV phenotypes. A total of 184 patients with biopsy-proven cranial GCA, 105 with LVV-GCA and 486 healthy controls were included in our study. We compared HLA-B phenotype frequencies between the three groups. HLA-B*15 phenotype was significantly increased in patients with classic cranial GCA compared to controls (14.7% versus 5.8%, respectively; p<0.01; OR [95% CI] =2.81 [1.54-5.11]). It was mainly due to the HLA-B*15:01 allele (12.5% versus 4.0%, respectively; p<0.01; OR [95% CI] =3.51 [1.77-6.99]) and remained statistically significant after Bonferroni correction. Similar HLA-B*15 association was observed in patients with the LVV-GCA (11.4% versus 5.8%, p=0.04, OR [95% CI] =2.11 [1.04-4.30]). This association was also mainly due to the HLA-B*15:01 allele (10.5% versus 4.0%, respectively; p=0.0054; OR [95% CI] =2.88 [1.19-6.59]). Noteworthy, the presence of HLA-B*15:01 together with HLA-DRB1*04:01 led to an increased risk of developing both cranial and extracranial LVV-GCA. Susceptibility to GCA is strongly related to the HLA region, regardless of the clinical phenotype of expression of the disease.

Investigating the association of Lamotrigine and Phenytoin‐induced Stevens‐Johnson syndrome/Toxic Epidermal Necrolysis with HLA‐B*1502 in Iranian population

Previous studies have found an association between HLA-B*1502 allele and lamotrigine-induced Stevens-Johnson syndrome (SJS)/ toxic epidermal necrosis (TEN) spectrum in Han Chinese populations. This study aims to investigate the association between HLA-B*1502 and lamotrigine- or phenytoin- induced SJS/TEN in an Iranian population. The medical records of twenty-eight lamotrigine-induced SJS/TEN patients and twenty-five lamotrigine-tolerant controls as well as eight phenytoin-induced SJS/TEN and twelve phenytoin-tolerant controls were extracted between March 2013 and March 2019 from the university hospitals in Mashhad, Iran. The presence of HLA-B*1502 allele was determined using real-time polymerase chain reaction (PCR). Among lamotrigine-induced patients with SJS/TEN, 11 (39.3%) patients tested positive for the HLA-B*1502 while only 3 (12.0%) of the lamotrigine-tolerant controls tested positive for this allele. The risk of lamotrigine-induced SJS/TEN was significantly higher in patients with HLA-B*1502, with an odds ratio (OR) of 4.74 [95% confidence interval (CI) 1.14-19.73, p=0.032]. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of HLA-B*1502 for lamotrigine-induced SJS/TEN was 39.29%, 88.00%, 78.57% and 56.41%, respectively. The HLA-B*1502 allele was present in 2 (25.0%) of phenytoin-induced SJS/TEN cases and 5 (41.7%) of the phenytoin-tolerant controls tested positive for HLA-B*1502 allele. The risk of phenytoin-induced SJS/TEN was not higher in the patients with HLA-B*1502 (OR=0.467 [95% confidence interval (CI) 0.065-3.34, p=0.642]). Lamotrigine-induced SJS/TEN is associated with HLA-B*1502 allele in an Iranian population but this is not the case for phenytoin-induced SJS/TEN.

M017 SEVERE PROTRACTED ALLOPURINOL-INDUCED DRESS/DIHS REQUIRING LONG-TERM, HIGH-DOSE IMMUNOSUPPRESSANTS

Allopurinol-related drug reaction with eosinophilia and systemic symptoms, also known as drug-induced hypersensitivity syndrome (DRESS/DiHS), may portend significant morbidity and mortality. Presence of HLA-B*58:01 and renal insufficiency are risk factors for allopurinol-induced DRESS/DiHS. Severe cases may require prolonged immunosuppressive therapy.

The role of HLA in Balkan endemic nephropathy

Balkan endemic nephropathy (BEN), a progressive chronic tubulointerstitial disease, occurs in the endemic focus of Croatia in a population of about 10,000 inhabitants. One of its most peculiar characteristics is a strong association with upper tract urothelial carcinoma (UTUC). Despite a high number of studies, currently there are insufficient data about the association of BEN and HLA genes. The aim of this study was to investigate the polymorphism of HLA-A, -B, and -DRB1 alleles and haplotypes among BEN patients and to determine whether an association between HLA and BEN exists. In this study, we investigated HLA-A, -B, and -DRB1 alleles and haplotypes in a population of patients with BEN (N=111) and matched healthy controls (N=190). All individuals were tested by PCR-SSO and PCR-SSP methods to assess the possible contribution of HLA alleles and haplotypes to the development of/protection from BEN. Our results showed a positive association between the presence of HLA-B*35:02 and DRB1*04:02 alleles and BEN (P=0.0179 and P=0.0151, respectively) in contrast to the protective effect of HLA-A*01:01, B*27:05 and B*57:01 alleles (P=0.0111, P=0.0330 and P=0.0318, respectively). Moreover, when BEN patients' HLA haplotypes were compared to controls, two haplotypes were associated with BEN susceptibility among Croatians (HLA-A*02:01~B*08:01~DRB1*03:01 and HLA-A*02:01~B*27:02~DRB1*16:01, P=0.0064 and P=0.0023, respectively), while haplotypes HLA-A*02:01~B*27:05~DRB1*01:01 and HLA-A*02:01~B*38:01~DRB1*13:01 each showed a possible protective effect (P=0.0495). Our results point toward genetic susceptibility to BEN and observed differences in both susceptible/protective HLA profiles indicate the necessity of further studies in order to elucidate the pathogenesis of this disease.

HLA-B[*]27 is significantly enriched in Nordic patients with psoriatic arthritis mutilans

The genetic contribution to psoriatic disease is substantial with a dominating influence of the HLA region. The profile of HLA class I genotypes likely contributes to shaping clinical phenotypes. Herein we aimed to explore such genotypes in cohorts of closely characterised subsets of psoriatic disease with special focus on psoriatic arthritis mutilans (PAM), a severe and rare form of psoriatic arthritis (PsA). Cohorts of patients with the diagnosis of psoriasis vulgaris with or without arthritis (n=1217), psoriasis without arthritis (n=534), psoriatic arthritis without mutilating disease (n=337) and psoriatic arthritis mutilans (n=63) were collected and genotyped for HLA class I and II genes, with standardised methodologies. Cases were compared with a healthy control population (n=2468). Case-only and case-control association tests were performed to address the hypothesis of genetic contribution to clinical phenotypes. The presence of HLA-B*27 was strikingly increased in PAM (45%) compared with PsA without mutilating disease (13%) and with healthy controls (13%). However, within the PAM population, HLA-B*27 did not correlate with clinical markers such as number of mutilating joints, radiographic scoring, disease duration and age of disease onset. HLA-B*27 emerges as an important genotype marker for PAM.

The occurrence of sacroiliitis in HLA-B*35-positive patients with undifferentiated spondyloarthritis. A cross sectional MRI study.

To investigate possible association between sacroiliitis and HLA-B*35 positivity. After excluding patients with axial spondyloarthritis and HLA-B*27 positivity, psoriasis inflammatory bowel disease, preceding infections, or juvenile type of spondyloarthritis, 110 patients were recruited with a diagnosis of undifferentiated axial spondyloarthritis. All of them had inflammatory back pain of short duration (3months to 2years) and 72 were HLA-B*35 positive. In order to determine if there is a possible association of sacroiliitis and HLA-B*35 positivity, all patients underwent MRI of sacroiliac joints. A statistically significant association between the detection of bone marrow edema at sacroiliac joints on MRI and HLA-B*35 positivity (χ2 = 6.25; p = 0.022) was found. A logistic regression analysis revealed that the presence of HLA-B*35 allele was associated with a 6 times greater chance of identifying bone marrow edema at sacroiliac joints on MRI (OR 6, 95% CI 1.3-27, p = 0.021). HLA-B*35 positivity was also associated with a 4.7 times greater chance of finding elevated CRP (OR 4.7, 95% CI 1-11.9, p = 0.047) and a 5 times greater chance of finding peripheral joint synovitis (OR 5, 95% CI 1.75-14.3, p = 0.003). HLA-B*35-positive patients had high disease activity (mean ± SD of Bath Ankylosing Spondylitis Disease Activity Index 6.1 ± 1.72 and Ankylosing Spondylitis Disease Activity Score C-reactive protein Index 3 ± 0.64) with a high degree of functional limitations (mean ± SD of Bath Ankylosing Spondylitis Functional Index 5.3 ± 2.16). The data clearly show the association between bone marrow edema on MRI at sacroiliac joints and HLA-B*35 allele in patients with undifferentiated spondyloarthritis. Further work is needed to understand how much this result may influence follow-up of these patients. Key Points • HLA-B*35 allele was associated with a 6 times greater chance of identifying bone marrow edema at sacroiliac joints on MRI in un-axSpa patients. • HLA-B*35 allele was also associated with a 4.7 times greater chance of finding elevated CRP and a 5 times greater chance of finding peripheral joint synovitis in un-axSpa patients. • HLA-B*35 allele could be a potential risk factor for developing sacroiliitis and axSpA.

Subacute Thyroiditis is Associated with HLA-B*18:01, -DRB1*01 and -C*04:01—The Significance of the New Molecular Background

Subacute thyroiditis (SAT) is a thyroid inflammatory disease whose pathogenesis is still not completely defined. Previous viral infection is considered to be a triggering factor in genetically predisposed individuals. In about 70% of patients, susceptibility to SAT is associated with the HLA-B*35 allele. The correlation between SAT and other human leukocyte antigens (HLA) has not yet been unequivocally demonstrated and the genetic background is still unknown in about 30% of patients. The purpose of our study was to perform HLA genotyping using a next-generation sequencing method, to find out whether alleles other than HLA-B*35 are correlated with SAT morbidity. HLA-A, -B, -C, -DQB1, -DRB1 were genotyped using a next-generation sequencing method in 1083 subjects, including 60 SAT patients and 1023 healthy controls. Among 60 patients diagnosed with SAT, 81.7% of subjects were identified as having allele HLA-B*35, 23.3% had HLA-B*18:01, 28.3% had HLA-DRB1*01 and 75.5% had HLA-C*04:01. These alleles occurred in the control group at frequencies of 10.2%, 7.2%, 12.9% and 12.5%, respectively. The differences were statistically significant, with p < 0.05. In addition to its previously described relationship with HLA-B*35, genetic susceptibility to SAT was associated with the presence of HLA-B*18:01, DRB1*01 and C*04:01. The alleles HLA-B*18:01 and DRB1*01 were independent SAT risk factors. The assessment of these four alleles allows the confirmation of genetic predisposition in almost all patients with SAT.

HLA-B*57:01 allele prevalence in treatment-Na\xefve HIV-infected patients from Colombia

BackgroundThe HLA-B*57:01 allele is associated with a hypersensitivity reaction to abacavir. Due to the lack of knowledge of HLA-B*57:01 prevalence in Colombia, routine screening is not performed and is not recommended by the national guidelines. We aimed to determine the prevalence of HLA-B*57:01 in HIV population from Colombia.MethodsThis cross-sectional study included naïve HIV-infected adults from 13 cities of the country. The presence of HLA-B*57:01 was determined by using SSP-PCR in blood samples. Prevalence rates were stratified by sex, race, and region of origin.ResultsHLA-B*57:01 allele prevalence in Colombian HIV-infected individuals was 2.7%. When stratifying for the race, the prevalence was 4% for whites, 2.6% for other race (mainly mestizo), and 1.9% for Afro-Colombians. The prevalence varied from 0% up to 11.4% depending on the department of origin. The highest prevalence rates were found in Caldas (11.4%), Antioquia (5%), Risaralda (4.8%), and Valle del Cauca (4.3%). When distributed by country zones, the central, with a racial predominance of Caucasians and mestizos, was the highest (6.0%, 0R = 4.1, CI 1.2–12.8, p = 0,016).ConclusionsThe overall prevalence of HLA-B*57:01 in Colombia was lower than the reported rates for other Latin American countries such as Brazil, Costa Rica, and Argentina, but similar in comparison to Chile and Mexico. The diversity in the racial and ethnic heritage shown in our data supports the recommendation to implement routine screening for the HLA-B*57:01 allele before initiation of abacavir-containing antiretroviral therapy in the Colombian HIV management guidelines.

The Risk of Recurrence of Subacute Thyroiditis Is HLA-Dependent

The frequency of recurrence of subacute thyroiditis (SAT) is rather high, reaching 20–30%. The reason for SAT relapse is still unknown. Recently, we have demonstrated the association between SAT and the presence of HLA-B*18:01, DRB1*01, and C*04:01, apart from the previously known HLA-B*35. The aim of the present study was to evaluate the correlation between SAT-associated HLA haplotypes and the risk of SAT recurrence. HLA-A, -B, -C, -DQB1 and -DRB1 were genotyped using a next-generation sequencing method in 49 SAT patients. The patients were divided into the following HLA groups: 1. HLA-B*35 and/or HLA-C*04, but without any other of the analyzed antigens; 2. HLA-DRB1*01, regardless of the co-presence of HLA-B*35 or -C*04:01, but without HLA-B*18:01; 3. HLA-B18 only, without any other antigen; 4. HLA-B*18:01 plus -B*35, regardless of the presence of any other analyzed antigens. The recurrence rate was compared between the groups. The recurrence rate was significantly increased in patients with HLA-B*18:01 plus HLA-B*35. In conclusion, the risk of SAT recurrence was HLA-dependent and the determining factor was the co-presence of HLA-B*18:01 and -B*35. In such high-risk patients, the steroid treatment regimen should be intensified with a slower dose reduction.

Sonographic Pattern of Subacute Thyroiditis Is HLA-Dependent.

Background: Since 1977 the susceptibility to SAT has been known to be HLA-B*35-related in ~70% of patients. Recently it has been demonstrated that SAT is associated with the presence of HLA-B*18:01 and DRB1*01, as well as with HLA-C*04:01. The association between the type of genetic SAT background and sonographic pattern of the disease has never been analyzed. The aim of the study was to evaluate the potential correlation between the presence of individual HLA haplotypes and the sonographic SAT pattern, and to provide the US characteristics of the analyzed SAT cases.Methods: HLA-A, -B, -C, -DQB1, and -DRB1 were genotyped using a next-generation sequencing method in 46 SAT patients. All patients were divided into the following groups according to the HLA haplotype: 1. HLA-B*35 and/or HLA-C*04, but without any other of the analyzed antigens; 2. HLA-DRB1*01, regardless of the co-presence of HLA-B*35 or C*04:01, but without HLA-B*18:01; 3. HLA-B*18:01 only, without any other of the analyzed antigens; 4. HLA-B*18:01 plus B*35, regardless of the presence of any other analyzed antigens. The US patterns of SAT thyroid lesions were compared among the groups.Results: The US image of SAT lesions in Groups 1 and 2 were similar. The typical SAT features for these groups were as follows: hypoechoic, strongly heterogeneous, bilateral, multiple areas, with decreased vascularization, usually oval with blurred margins, infrequently affecting the whole lobe, or having nodule-like pattern. Several features of Group 3 were different from the other groups. In 60% of cases lesions were rather homogeneous, and in 100%–hypoechoic, in 80% of patients there was only one unilateral single SAT area filling the whole affected lobe. On the contrary to the other groups, in Group 4 no lesion was oval in shape.Conclusions: Our results provide for the first time the evidence that the US pattern of SAT lesions depends on HLA, and the determining factor is the presence of HLA-B*18:01. The deviations from the typical SAT US image are mostly pronounced in patients with the presence of only HLA-B*18:01, without any other analyzed haplotype. Further research is necessary to explain this phenomenon.

Salmonella exploits HLA-B27 and host unfolded protein responses to promote intracellular replication

ObjectiveSalmonella enterica infections can lead to Reactive Arthritis (ReA), which can exhibit an association with human leucocyte antigen (HLA)-B*27:05, a molecule prone to misfolding and initiation of the unfolded protein...

Distribution of HLA-B Locus Antigens in Patients with Psoriatic Arthritis in Bangladesh

This study was designed to investigate the distribution of HLA-B locus antigens in patients with psoriatic arthritis (PsA) in Bangladesh and identify HLA markers related to disease manifestation in PsA. HLA-B typing was carried out by polymerase chain reaction (PCR) with sequence specific primers in a group of 50 consecutive PsA patients. The reports of HLA-B locus antigens typing were collected from 50 ages and sex matched unrelated healthy donors as controls. A total of 17 HLA-B locus antigens were determined in both patients and controls. The most common antigen was B*15 (34%) followed by B*07 (26%), B*27 (24%), B*38 (20%). Human leukocyte antigens B*07, B*27 and B*38 alleles were found to be significantly prevalent in PsA patients compared with healthy controls. We found a statistically significant association between spondylitis pattern and the presence of HLA-B*27. PsA in Bangladeshi patients seems to be associated with the presence of B*07, B*27 and B*38 alleles.&#x0D; Bangladesh J Med Microbiol 2018; 12 (2): 14-20

CYP2C9 polymorphisms in epilepsy: influence on phenytoin treatment.

Phenytoin (PHT) is an antiepileptic drug widely used in the treatment of focal epilepsy and status epilepticus, and effective in controlling focal seizures with and without tonic–clonic generalization and status epilepticus. The metabolization of PHT is carried out by two oxidative cytochrome P450 enzymes CYP2C9 and CYP2C19; 90% of this metabolization is done by CYP2C9 and the remaining 10% by CYP2C19. Genetic polymorphism of CYP2C9 may reduce the metabolism of PHT by 25–50% in patients with variants *2 and *3 compared to those with wild-type variant *1. The frequency distribution of CYP2C9 polymorphism alleles in patients with epilepsy around the world ranges from 4.5 to 13.6%, being less frequent in African-Americans and Asians. PHT has a narrow therapeutic range and a nonlinear pharmacokinetic profile; hence, its poor metabolization has significant clinical implications as it causes more frequent and more serious adverse effects requiring discontinuation of treatment, even if it had been effective. There is evidence that polymorphisms of CYP2C9 and the use of PHT are associated with an increase in the frequency of some side effects, such as cerebellar atrophy, gingival hypertrophy or acute cutaneous reactions. The presence of HLA-B*15:02 and CYP2C9 *2 or *3 in the same patient increases the risk of Stevens–Johnson syndrome and toxic epidermal necrolysis; hence, PHT should not be prescribed in these patients. In patients with CYP2C9 *1/*2 or *1/*3 alleles (intermediate metabolizers), the usual PHT maintenance dose (5–10 mg/kg/day) must be reduced by 25%, and in those with CYP2C9 *2/*2, *2/*3 or *3/*3 alleles (poor metabolizers), the dose must be reduced by 50%. It is controversial whether CYP2C9 genotyping should be done before starting PHT treatment. In this paper, we aim to review the influence of CYP2C9 polymorphism on the metabolization of PHT and the clinical implications of poor metabolization in the treatment of epilepsies.

The association of HLA B*15:02 allele and Stevens–Johnson syndrome/toxic epidermal necrolysis induced by aromatic anticonvulsant drugs in a South Indian population

The presence of HLA-B*15:02 allele is considered a risk factor for development of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in patients taking aromatic anticonvulsant drugs like carbamazepine and phenytoin. The genetic association is ethnicity specific. Testing for HLA-B*15:02 allele is suggested as a prerequisite before starting carbamazepine in certain ethnic groups. There are only a few/no studies from south India on HLA association of SJS/TEN. To identify any association between HLA-B*15:02 allele and SJS/TEN induced by carbamazepine/phenytoin among native population. METHODS (INCLUDING SETTINGS, DESIGN, AND STATISTICAL ANALYSIS USED): A case-control study done in a tertiary care center at Kottayam in Kerala state of south India. Cases were 12 native patients who developed SJS/TEN owing to aromatic anticonvulsant drugs (phenytoin - 8; carbamazepine - 4), and controls were 11 persons tolerant to these drugs from unrelated families of the same ethnic group. HLA-B typing was done by PCR SSP method. There was only one HLA-B*15:02 carrier among cases and controls. He/she had SJS/TEN induced by carbamazepine. Association of HLA-B*15:02 with phenytoin-induced SJS/TEN is rare in the population studied. The one limitation of the study was the small sample size.