Increased risk of malignancy in HLA-B27-positive patients with ankylosing spondylitis requiring biologics for sustained inflammation: A long-term, single-center retrospective study.

OBJECTIVES: To assess the link between the administration of biologic disease-modifying antirheumatic drugs (bDMARDs) and the risk of malignancy in human leukocyte antigen B27 (HLA-B27)-positive patients with ankylosing spondylitis (AS) experiencing sustained inflammation. METHODS: Between 2006 and 2021, 1445 HLA-B27-positive patients with AS were retrospectively evaluated. Among them, 112 patients required bDMARD therapy. The study compared conventional therapy with bDMARDs and investigated the risk factors for developing malignancies. RESULTS: During 8253 patient-years of follow-up, 38 (2.6%) patients developed various malignancies, including lung, liver, breast, and colon cancer. The risk of malignancy was significantly higher in the bDMARD-treated group compared to PS-matched groups receiving conventional synthetic DMARDs (csDMARD) and non-steroidal anti-inflammatory drugs. The cumulative risk of malignancies increased significantly after 6 years of follow-up. All patients who developed malignancy after bDMARD therapy received tumor necrosis factor-α inhibitors. Requiring bDMARD therapy, requiring bDMARDs in combination with csDMARD therapy, and being diagnosed with AS after 30 years of age were independent risk factors for developing malignancy. CONCLUSIONS: HLA-B27-positive AS patients with sustained inflammation requiring biologic therapy, particularly if diagnosed after age 30, may have an increased risk of malignancy. Regular cancer screenings are advisable for these patients while undergoing biologic treatment.

High-Throughput and Automated Detection of HLA-B*27 Using the LabTurboTM AIO System.

The adoption of an automated system can decrease the hands-on time requirements in a clinical laboratory setting. For the detection of HLA-B*27, implementing a high-throughput and fully automated system has several advantages over using manual methods. Therefore, this study aimed to evaluate automation efficiency for the detection of HLA-B*27. Peripheral blood samples were obtained from 50 participants, and DNA was isolated from these samples. A Pharmigene PG27 detection kit was used for the qualitative detection of HLA-B*27. The performances of the semi-automated and fully automated LabTurboTM AIO systems in the detection of HLA-B*27 were compared. The mean absorbance (optical density) values for the MaelstromTM 8 and LabTurboTM AIO systems were found to be 1.88 and 1.9, respectively. The housekeeping gene was amplified and quantified using a real-time PCR assay across all DNA extracts to check the quality of the extracted human DNA. The results were expressed as the cycle threshold (Ct) values for all DNA extracts from both platforms. The mean Ct values for the Roche Cobas z480 and LabTurboTM AIO systems were found to be 22.7 and 20.4, respectively. This study demonstrated that the semi-automated method and the LabTurboTM AIO system yield consistent results for the detection of HLA-B*27. However, compared to the semi-automated method, the LabTurboTM AIO system provides standardized procedures, avoids manual handling, and improves turnaround time.

Inhibition of ERAP1 represses HLA-B27 free heavy chains expression on polarized macrophages and interrupts NK cells activation and function from ankylosing spondylitis.

BACKGROUND: We aimed to assess if Endoplasmic reticulum aminopeptidase 1 (ERAP1) polymorphisms might impress Human leukocyte antigen (HLA)-B27-free heavy chains (FHCs) expression on macrophages and eventually NK cell activation in Ankylosing spondylitis (AS). METHODS: Blood samples were obtained from 10 HLAB27+ patients with protective and 10 HLAB27+ patients with non-protective genotype. Monocytes were isolated and polarized toward M1 and M2 macrophages. ERAP1 was inhibited in macrophages, which were then co-cultured with autologous NK cells. RESULTS: Expression of HLA-B27-FHCs on M1 and M2 macrophages was reduced in patients with protective ERAP1 genotype. Co-culturing ERAP1-inhibited M1 macrophages and NK cells from patients with protective genotype resulted in downmodulation of CD69 and CD107a markers on NK cells and reduced number of IFN-γ+ NK cells compared to that of patients with non-protective genotypes. CONCLUSION: Inhibition of ERAP1 activity, by diminishing NK activation, may have therapeutic value in treating AS patients.

Association between HLA-B*27:04 and genetic susceptibility to ankylosing spondylitis in Hunan Province. / 湖南地区携带HLA-B*27꞉04ç­‰ä½åŸºå› äººç¾¤ä¸Žå¼ºç›´æ€§è„ŠæŸ±ç‚Žçš„æ˜“æ„Ÿæ€§å ·æœ‰å¼ºç›¸å ³æ€§ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Human leukocyte antigen (HLA) B27 is a susceptibility allele of ankylosing spondylitis (AS), and HLA-B27 antigen typing is an important indicator for clinical diagnosis of AS, but current typing methods such as sequence specific primer polymerase chain reaction (PCR-SSP) still possess limitation. Therefore, this study aims to analyze the correlation between B27 subtypes and susceptibility to AS in Hunan Province by applying high-resolution polymerase chain reaction-sequence-based typing (PCR-SBT). METHODS: Peripheral blood of 116 patients with suspected AS (suspected AS group) and 121 healthy volunteers (control group) admitted to the Second Xiangya Hospital from January 2020 to December 2020 were collected for HLA-B genotyping by PCR-SBT. Among the patients in the suspected AS group, 23 patients were finally diagnosed with AS (confirmed AS group), and the remaining 93 undiagnosed patients served as the non-confirmed AS group. PCR-SBT and PCR-SSP were used to detect HLA-B27 typing in 116 patients with suspected AS, and the results of the 2 methods were compared. RESULTS: The HLA-B27 allele frequency in the suspected AS group was significantly higher than that in the control group [11.63% vs 2.48%; P<0.001, odds ratio (OR)=5.18, 95% confidence interval (CI) 2.097 to 12.795]. B*27:04, B*27:05, B*27:06, and B*27:07 were detected in the suspected AS group and the control group. The frequency of the B*27:04 allele in the suspected AS group was significantly higher than that in the control group (9.48% vs 1.24%; P<0.001, OR=8.346, 95% CI 2.463 to 28.282). The positive rate of B27 in the suspected AS group and the confirmed AS group (B27+/+ and B27+/-) was significantly higher than that in the control group (χ2=16.579, P<0.001; χ2=94.582, P<0.001, respectively). Among the confirmed AS group, 21 were HLA-B27 carriers, and the B27 positive rate in the confirmed AS group was 91.3%. PCR-SBT could achieve high resolution typing of the HLA-B gene locus, with higher sensitivity, specificity, positive predictive value, negative predictive value, and accuracy than PCR-SSP. CONCLUSIONS: PCR-SBT typing analysis shows a strong correlation between HLA-B * 27:04 and AS in Hunan province. The PCR-SBT method can be used as the preferred option for the auxiliary diagnosis of clinical AS.

Clinical Characteristics of Patients With Psoriatic Spondylitis Versus Those With Ankylosing Spondylitis: Features at Baseline Before Biologic Therapy.

BACKGROUND: Clinical characteristics and manifestations of psoriatic arthritis (PsA) have been extensively studied in western countries, yet data of Korean patients with PsA are very limited. We aimed to investigate the clinical traits of patients with PsA and dissect the characteristics of those with axial involvement. METHODS: In this observational study, we analyzed clinical data of 109 patients with PsA who were enrolled in the Korean College of Rheumatology Biologics and Targeted Therapy registry between December 2012 and March 2022 at the time point of initiating or switching to a biologic agent. Data from 2,221 patients with ankylosing spondylitis (AS) registered during the same period were also analyzed. We divided patients with PsA into patients with or without axial involvement and then added AS patients with psoriasis (total three subgroups) for comparative analyses. RESULTS: Asymmetric oligoarthritis was the most common clinical manifestation in patients with PsA, followed by symmetric polyarthritis and spondylitis. Our analysis indicated that methotrexate and sulfasalazine were the two most prescribed disease-modifying antirheumatic drugs for patients with PsA before starting biologic therapy. The patients with psoriatic spondylitis had more peripheral joint involvement (P = 0.016), less prior uveitis (P < 0.001), and lower human leukocyte antigen B27 (HLA-B27) positivity (P < 0.001) than the AS patients with psoriasis. Furthermore, syndesmophytes and radiographic sacroiliitis were prevalent among patients with PsA and AS patients with psoriasis who had the HLA-B27 gene. CONCLUSION: Our study shows that the degree of peripheral arthritis is less severe in Korean patients with PsA who require biologics and reestablishes that psoriatic spondylitis is a common and important clinical pattern in Korean patients with PsA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01965132.

Occurrence of human leukocyte antigen B51-related ankylosing spondylitis in a family: Two case reports.

BACKGROUND: Ankylosing spondylitis (AS) is strongly associated with the human leukocyte antigen (HLA) B27 haplotype. In regions where conventional polymerase chain reaction for HLA typing is available for antigens such as HLA B27 or HLA B51, it is common to perform the HLA B27 test for evaluation of AS. While HLA B27-associated clustered occurrences of AS have been reported in families, we report the first case series of HLA B51-related occurrences of AS in a family. CASE SUMMARY: A father and his daughters were diagnosed with AS and did not have the HLA B27 haplotype. Although they were positive for HLA B51, they exhibited no signs of Behçet's disease (BD). Of the five daughters, one had AS, and three, including the daughter with AS, were positive for HLA B51. The two daughters with the HLA B51 haplotype (excluding the daughter with AS) exhibited bilateral grade 1 sacroiliitis, whereas the daughters without the HLA B51 haplotype did not have sacroiliitis. Thus, this Korean family exhibited a strong association with the HLA B51 haplotype and clinical sacroiliitis, irrespective of the symptoms of BD. CONCLUSION: It is advisable to check for HLA B51 positivity in patients with AS/spondyloarthropathy who test negative for HLA B27.

Secukinumab in non-radiographic axial spondyloarthritis: subgroup analysis based on key baseline characteristics from a randomized phase III study, PREVENT.

BACKGROUND: To investigate the efficacy of secukinumab in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) grouped by disease activity as assessed by C-reactive protein (CRP) levels and/or magnetic resonance imaging (MRI) scores, human leukocyte antigen (HLA)-B27 status, and sex. METHODS: The phase III PREVENT study randomized (1:1:1) 555 patients to receive subcutaneous secukinumab 150 mg with (LD) or without (NL) loading dose or placebo weekly, followed by every 4 weeks starting at week 4. Here, we report the results of a post hoc analysis reporting the efficacy outcomes (pooled secukinumab) to 16 weeks by CRP, MRI, HLA-B27, and sex. RESULTS: Efficacy differences between the secukinumab and the placebo groups were highest in the CRP+, MRI+, HLA-B27+, and male subgroups, particularly for Ankylosing Spondylitis Disease Activity Score-CRP inactive disease and Assessment of SpondyloArthritis international Society (ASAS) partial remission outcomes. ASAS40 response rates in the CRP+/MRI+ subgroup was 52.3% (secukinumab) versus 21.8% (placebo; P < 0.0001) at week 16. ASAS40 response rates (secukinumab versus placebo) were 43.9% versus 32.6% in HLA-B27+, 32.7% versus 16.4% in HLA-B27- subgroups, 51.2% versus 30.8% in male, and 31.7% versus 25.3% in female patients, respectively. CONCLUSIONS: Secukinumab improved the signs and symptoms of nr-axSpA across patients grouped by CRP (+/-) and/or MRI (+/-) status, HLA-B27 (+/-) status, and sex. The highest treatment differences between secukinumab and placebo were observed in patients with both elevated CRP and evidence of sacroiliitis on MRI. Treatment difference was minimal between HLA-B27 (+) and (-) subgroups. Male patients had higher relative responses than female patients. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02696031 . Registered on 02 March 2016.

Association of the genetic variants in the endoplasmic reticulum aminopeptidase 2 gene with ankylosing spondylitis susceptibility.

BACKGROUND: Genetic polymorphisms in the endoplasmic reticulum aminopeptidase gene ERAP2 has been attributed with the etiopathogenesis of ankylosing spondylitis (AS). Here we assessed the association of ERAP2 gene single nucleotide polymorphisms (SNPs) with AS predisposition in Iranian patients and determined their effect on the inflammatory state of the patients. METHODS: For genotyping of rs2548538, rs2287988, and rs17408150 SNPs using a real-time allelic discrimination approach, DNA was extracted from the whole blood of 250 AS patients and 250 healthy individuals. RNA of the peripheral blood mononuclear cells was separated, cDNA was synthesized, and transcriptional levels of cytokines, including interleukin (IL)-17A, IL-23, IL-10, and transforming growth factor-ß, were measured. Enzyme-linked immunosorbent assay was used to measure the serum concentration on the cytokines. RESULTS: Three ERAP2 gene SNPs were not associated significantly with AS risk. Nonetheless, rs2287988 and rs17408150 SNPs showed statistically significant association with susceptibility to the disease in those AS patients who were positive for human leukocyte antigen (HLA)-B27. Transcriptional level and serum concentration of IL-17A and IL-23 were higher, but those of IL-10 were lower in both AS patients and the HLA-B27-positive patient group relative to the control group. Nevertheless, ERAP2 gene SNPs in the HLA-B27-positive AS patients did not affect the transcription level and serum concentration of cytokines. CONCLUSIONS: ERAP2 gene rs2287988 and rs17408150 SNPs are associated with susceptibility to AS, but they are probably not determining the levels of IL-17A, IL-23, and IL-10 in this disease.

The Involvement of Temporomandibular Joint in Psoriatic Arthritis: A Report of a Rare Case.

Psoriatic arthritis (PsA) is a chronic inflammatory condition affecting psoriatic patients. Its clinical manifestations in patients can vary over time, advancing from one joint to the next with an intermittent pattern of exacerbation and remission. The condition shares similar manifestations with rheumatoid arthritis (RA), ankylosing spondylitis, and reactive arthritis; hence, a comprehensive examination is required for a proper diagnosis and management. It is associated with an increased risk of comorbidities affecting patients' well-being. There have been few incidences of involvement extending to the temporomandibular joint (TMJ), but a proper record needs to be maintained to evaluate its part in PsA. In this report, we present a case of PsA in which the patient complained of ear pain and was discovered to have early alterations in the TMJ.

Endoplasmic reticulum aminopeptidase 2 gene single nucleotide polymorphisms in association with susceptibility to ankylosing spondylitis in an Iranian population.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic autoimmune disease, in which genetic polymorphisms are critically important in establishing inflammatory state. Endoplasmic reticulum aminopeptidase (ERAP) 2 gene has been implied to be involved in AS etiopathogenesis. The current study evaluated the association of ERAP2 gene single nucleotide polymorphisms (SNPs) with susceptibility to AS in an Iranian population. METHODS: Two hundred and forty AS patients and 240 healthy individuals were recruited. DNA extraction was performed from whole blood samples and RNA content was isolated from peripheral blood mononuclear cells (PBMCs). Real-time allelic discrimination approach was exerted to genotype all subjects for rs2910686, rs2248374, and rs2549782 SNPs. After cDNA synthesis, mRNA expression of cytokines was determined. Enzyme-linked immunosorbent assay (ELISA) was exerted to evaluate the cytokine levels in serum of participants. RESULTS: None of the SNPs were associated with AS risk in the whole population. However, allele and heterozygote genotype of rs2910686 SNP were associated significantly with higher risk of AS in Human leukocyte antigen (HLA)-B27 positive group. mRNA expression and serum concentrations of interleukin (IL)-17A, IL-23, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α was increased in AS patients compared with controls. Nonetheless, mRNA expression and serum levels of cytokines was not significantly different among HLA-B27 positive AS patients with different three genotypes for rs2910686 SNP. CONCLUSIONS: AlthoughERAP2 gene rs2910686 polymorphism was significantly associated with increased risk of AS susceptibility, it might not be involved in regulation of the inflammatory cytokines during AS pathogenesis.

Common incidental findings on sacroiliac joint MRI in children clinically suspected of juvenile spondyloarthritis.

PURPOSE: To determine the prevalence of incidental findings on sacroiliac (SI) joint MRI in children clinically suspected of Juvenile Spondyloarthritis (JSpA). METHODS: In this retrospective multi-center study of 540 children clinically suspected of JSpA who underwent MRI of SI joints from February 2012 to May 2018, the prevalence of sacroiliitis and other incidental findings was recorded. RESULTS: In 106/540 (20 %) children MRI features of sacroiliitis were present. In 228 (42 %) patients MRI showed at least one incidental finding other than sacroiliitis. A total of 271 abnormal findings were reported. The most frequent incidental findings were at lumbosacral spine (158 patients, 29 %) and hip (43 patients, 8 %). The most common incidental finding was axial degenerative changes, seen in 94 patients (17 %). Other less frequent pathologies were: simple (bone) cyst in 15 (2,8 %) patients; enthesitis/tendinitis in 16 (3 %) patients; non-specific focal bone marrow edema (BME) away from SI joints in 10 (1,9 %) patients; ovarian cysts in 7 (1,3 %) patients; BME in the course of chronic recurrent multifocal osteomyelitis (CRMO) in 4 (0,7 %) patients; muscle pathology in 4 (0,7%) patients; benign tumors in 3 (0,6 %) patients; (old) fractures in 3 (0,6 %) patients; bony apophyseal avulsion in 2 (0,4 %) patients and malignant tumors in 2 (0,4 %) patients. CONCLUSION: Incidental findings are common on MRI of the SI joints in children clinically suspected of JSpA, particularly at the lumbar spine and hips. They are seen even more frequently than sacroiliitis and can be relevant, as some will have clinical significance or require treatment.

Association Between Human Leukocyte Antigen-B*27 and Pathogenesis in Seronegative Spondyloarthropathies in Federation of Bosnia and Herzegovina.

OBJECTIVES: This study aims to investigate the low-resolution human leukocyte antigen (HLA)-B locus polymorphisms between unrelated healthy individuals and patients with diagnosis of seronegative spondyloarthropathies and determine risky and protective allelic groups and genotypes. PATIENTS AND METHODS: The study included 104 healthy control individuals (52 males, 52 females; median age 43 years; range 2 to 76 years) and 96 patients (43 males, 53 females; median age 28.5 years; range 2 to 67 years) diagnosed with: ankylosing spondylitis (AS) (n=19), reactive arthritis (n=19), psoriatic arthritis (n=28) and undifferentiated spondyloarthropathies (n=30). Genomic deoxyribonucleic acid was extracted from peripheral blood to detect allelic groups of HLA class I and II. Single-specific-primer polymerase chain reaction was used for HLA genotyping and visualization of products after their separation on 1.5% agarose gel for horizontal gel electrophoresis. RESULTS: Significantly increased frequency was found for HLA-A*02 and HLA-B*27 allelic variants in all groups of patients. The increased frequency of the HLA-B*35 allelic group in the control group represents the protective gene variant for the occurrence of AS. The predisposing genotype (HLA-B*27/B*44 and B*27/B*51) for the onset of disease was only found in AS patients. CONCLUSION: This study shows the strong association of HLA-B*27 antigen with spondyloarthropathies, which is considered a risk variant of the gene for the onset of disease. Protective and risky allelic variants and genotypes are rare and their detection as well as increased frequency are possible if larger numbers of patients are involved.

Clinical Characteristics and Prognostic Factors in Ankylosing Spondylitis Associated Uveitis.

PURPOSE: To identify the clinical features and prognostic factors of uveitis associated with ankylosing spondylitis (AS). METHODS: This retrospective, interventional case series study reviewed the medical records of 91 AS patients with uveitis. RESULTS: The characteristics of AS-associated uveitis included male preponderance (70%), average onset in the fourth decade, unilateral manifestation (87.9%), and vitreous involvement or retinal vascular leakage (36.3%). All patients had acute anterior uveitis. The best corrected visual acuity in logMAR improved from 0.8 ± 0.3 to 0.1 ± 0.2. The use of biologic agents was the only significant factor in the multivariate analysis. Patients with vitreous involvement/retinal vascular leakage were more likely to use systemic/peribulbar steroids for inflammation control, and achieved equally favorable visual outcome as in those without vitreous involvement/retinal vascular leakage. CONCLUSION: The clinical characteristics and profile of visual prognostic factors suggest an association between the severity of ocular inflammation and systemic disease.

PD-1 Polymorphisms Are Associated with Susceptibility of Acute Anterior Uveitis in Chinese Population.

Acute anterior uveitis (AAU) is an ordinary type of uveitis, which is an autoimmune disease produced by T cells. Programmed apoptosis protein 1 (PD-1) is a vital negative regulatory protein of immune tolerance. We detect the single nucleotide polymorphisms (SNPs) rs41386349, rs10204525, and rs2227982 of PD-1 to investigate the correlation between PD-1 polymorphisms and AAU. A total of 166 AAU patients and 263 controls were recruited in this case-control study. Compared with controls, the frequencies of the GG genotypes were higher in rs10204525 in AAU patients (p = 0.012). There were obvious increases in frequencies of the TT genotypes in rs2227982 and the GG genotypes in rs10204525 in human leukocyte antigen (HLA)-B27-negative AAU patients compared with controls (p = 0.03; p = 0.015, respectively). There were also increases in frequencies of TT genotypes in rs2227982 and the GG genotypes in rs10204525 in the patients without ankylosing spondylitis (AS) when compared with controls (p = 0.021; p = 0.003, respectively). Furthermore, the frequencies of TT genotypes in rs2227982 were higher in female patients diagnosed with AAU than with control group (p = 0.033). Our results showed that SNPs rs2227982 and rs10204525 were interrelated to AAU; the influence on AAU could be related with gender, HLA-B27, and AS status.

Association analysis of ERAP1 gene single nucleotide polymorphism in susceptibility to ankylosing spondylitis in Iranian population.

Background Ankylosing spondylitis (AS) is a debilitating spondyloarthropathy that has been associated with variation in several genes. Human leukocyte antigen (HLA)-B27 constructs an impaired structure, culminating in recognition and activation of immune system. Impaired function of Endoplasmic reticulum aminopeptidase (ERAP) 1, which primes peptides to be loaded in HLA molecules, has strongly been associated with AS proneness. Here, we intended to investigate the possible association of ERAP1 gene single nucleotide polymorphisms (SNPs) with AS susceptibility in Iranian patients. Methods Two-hundred and twenty AS patients and 220 healthy controls were enrolled in this study. DNA was extracted from blood samples and then was genotyped for rs27044, rs17482078, and rs10050860 polymorphism by SSP-PCR approach. Results It was seen that G allele and GG genotype of rs27044 SNP significantly increased the risk of AS that was even stronger in HLA-B27 positive patients. Moreover, the T allele and TT genotype of rs10050860 polymorphism were associated with increased risk of the disease in both all and HLA-B27 positive AS group. Two haplotypes were associated with the risk of AS and there was linkage disequilibrium between SNPs. Two SNPs were associated with clinicopathological manifestations of AS subjects. Conclusions This association study replicated the role ofERAP1 gene polymorphisms with the risk of AS in an Iranian population.

The effect of methotrexate and sulfasalazine on the course of HLA-B27-positive anterior uveitis: results from a retrospective cohort study.

PURPOSE: To investigate the effect of methotrexate (MTX) or sulfasalazine (SSZ) on the course of HLA-B27-positive, remitting acute anterior uveitis (AAU). METHODS: Forty-six patients with HLA-B27-positive AAU with or without associated systemic rheumatic disease either receiving MTX (n = 20), SSZ (n = 13), or no systemic immunomodulating treatment (Ctrl; n = 13) were studied retrospectively. Best-corrected visual acuity (BCVA), AAU relapse rate, and occurrence of uveitis-related ocular complications were analyzed at baseline (BL) and at 12-month follow-up (FU). RESULTS: Groups did not differ regarding age, gender, and presence of associated systemic diseases. BCVA at baseline was significantly worse in patients receiving MTX (logMAR 0.39 ± 0.4) than in those treated with SSZ (0.17 ± 0.2; P = 0.05) or in controls (Ctrl; 0.14 ± 0.2; P = 0.009). At the 12-month endpoint, MTX treatment was associated with significantly improved BCVA (0.18 ± 0.4 logMAR; P = 0.004). In contrast, BCVA did not significantly change in patients treated with SSZ (0.17 ± 0.3 logMAR) or in the controls (0.11 ± 0.2 logMAR). The annual uveitis relapse rate significantly decreased with MTX (BL 3.6 ± 2.4 relapses to FU 0.7 ± 0.8; P = 0.0001) and SSZ (BL 3.6 ± 1.9 to FU 1.8 ± 2.4, P < 0.01), but not in the controls (BL 1.9 ± 1.4 vs 1.9 ± 1.7 FU). The complication rate was slightly reduced with MTX (BL 1.75 ± 1.2 complications present versus FU 1.3 ± 1.2, P = 0.09) but not with SSZ (BL 0.9 ± 0.8 to FU 1.3 ± 1.4; P = 0.4) or in the controls (BL and FU 1.0 ± 0.95; P = 0.7). CONCLUSIONS: MTX and SSZ reduced the uveitis relapse rate in HLA-B27-positive AAU patients, with MTX showing a beneficial effect on AAU-related macular edema.

A case of human leukocyte antigen B-27-associated ocular hypotony successfully treated with golimumab.

A 42-year-old male presented to us after an episode of acute anterior human leukocyte antigen (HLA)-B27-associated uveitis, and intraocular pressure (IOP) in the right eye was 4 mmHg. Ultrasound biomicroscopy revealed ciliary body edema with supraciliary effusion. He was on a frequent topical corticosteroid, and oral steroid in addition to receiving a periocular injection depot corticosteroid 20 days back. He was started on treatment with subcutaneous golimumab (GLM). After a month, his IOP in the right eye was 14 mm of Hg with UBM showing resolution of ciliary body edema. GLM can be useful in the management of steroid-resistant cases of HLA B-27-associated ocular hypotony.

Optimization of an in-house PCR method for the detection of HLA-B*27 alleles.

The association of spondyloarthropathies with different alleles of human leukocyte antigen (HLA) B*27 is well established. Different subtypes of HLA-B*27 may be linked with different ethnic groups, distinct clinical manifestations, specific age of onset and different prognoses. Polymerase chain reaction with sequence specific primers (PCR-SSP) is the most frequently adapted molecular method used for the recognition of HLA-B*27-specific DNA sequences. The aim of the present study was to standarise an in-house protocol of PCR-SSP for HLA-B*27 allele detection for use in the Armed Forces Institute of Pathology (AFIP), Pakistan, with consideration of its cost effectiveness. A total of 49 individual samples were included, comprising 10 transplant samples determined to be HLA-B*27-negative by PCR-SSP and 39 HLA-B*27-positive samples determined by flow cytometry, obtained from patients who were symptomatic and referred for HLA-B*27 testing. By altering each variable individually, an in-house PCR-SSP protocol was optimized to amplify common HLA-B*27 alleles (2701-2721, 2723-2730). To discriminate B*27 from all other HLA-B alleles, a low-resolution HLA-B typing set with a 96 PCR-SSP primer mixture was used in conjunction. Among the 39 HLA-B*27-positive specimens, 31 (79%) were detected as positive by PCR-SSP, with the remaining samples failing due to a sub-optimized protocol and/or low DNA concentration. Additionally, there was complete concordance between flow cytometry and in-house PCR, and the sensitivity and specificity of the PCR-SSP were determined to be 100%. In conclusion, in-house SSP-PCR is, standard method for the detection of HLA-B*27 alleles. The determination of associations between specific HLA-B*27 alleles and AS may aid to identify individuals at higher risk of developing the disease. Furthermore, the identification of individuals at risk may aid to adapt preventive strategies.

Human Leukocyte Antigen-B27: The Genetic Predisposition Leading to Reactive Arthritis during Induction Phase Chemotherapy for Acute Myeloid Leukemia.

We report a case of reactive arthritis (ReA) during induction phase chemotherapy of a 15-year-old male patient with acute myeloid leukemia (AML) M4 with inv(16), most probably due to a genetic predisposition of being human leukocyte antigen b27 (HLA-B27) positive. The episode of ReA recurred during consolidation therapy; however, the patient was asymptomatic after the completion of treatment. The link between HLA-B27 and a large family of inflammatory rheumatic diseases is a well-established fact, but interestingly, there is also a molecular link between HLA-B27 and hematological malignancies. This case brings to our notice, the common immunological, molecular, and microbiological link between AML, HLA-B27, and ReA. It also emphasizes the fact that clinicians should have a high index of suspicion of HLA-B27 positivity, if a case of AML develops arthritis during chemotherapy, since early introduction of immunosuppressive medications for arthritis may reduce morbidity and prevent delay in the administration of further chemotherapy cycles.

Genetic association between TAP1 and TAP2 polymorphisms and ankylosing spondylitis: a systematic review and meta-analysis.

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic inflammatory joint disease. The transporter associated with antigen processing (TAP) has been identified to play an important role in immune response as well as the HLA-associated diseases. The aim of our meta-analysis was to investigate the contribution of TAP (TAP1 and TAP2) polymorphisms to the risk of AS. METHODS: Meta-analyses were performed between 2 polymorphisms in TAP1 (TAP1-333, -637) and 3 polymorphisms in TAP2 (TAP2-379, -565, and -665) and AS. RESULTS: The meta-analyses were involved with 6 studies with 415 cases and 659 controls. Significant association was found between TAP1-333Val, TAP1-637Gly, and TAP2-565Thr and AS compared with combined control group (TAP1-333Val: p = 0.009, OR = 1.40, 95% CI 1.09-1.80; TAP1-637Gly: p = 0.002, OR = 1.48, 95% CI 1.15-1.91; p = 0.03, OR = 1.38, 95% CI 1.04-1.84). Subgroup analysis shown that significant association was only found in AS when compared with HLA-B27-negative controls (TAP1-333Val: p = 0.004, OR = 1.53, 95% CI 1.14-2.06; TAP1-637Gly: p = 0.004, OR = 1.52, 95% CI 1.15-2.02; p = 0.02, OR = 1.56, 95% CI 1.09-2.24), but not in AS when compared with HLA-B27-positive controls (p > 0.05). Moreover, no significant associations were found between haplotypes in TAP1 and TAP2 in both the combined and the subgroup analyses (p > 0.05). CONCLUSIONS: TAP1-333Val, TAP1-637Gly, and TAP2-565Thr were likely to be associated with AS.