Here, we report the results of the first histocompatibility proficiency testing (PT) performed by the Korean Association of External Quality Assessment Service in 2018. The directly prepared PT specimens of whole blood, sera, and mononuclear cell suspensions were distributed to participants biannually. The number of participants was comparable to that in the previous external PT program, and the response rate was 88%–100%. The accuracy rates for human leukocyte antigen (HLA) A, B, C, DR, and DQ low and high resolution typing were 100%/100%, 100%/98%, 100%/99%, and 99%/98%, respectively; HLA-B27 typing, 99.1%; T cell and B cell crossmatching, 3.1% and 6.0%, respectively; and HLA antibody screening and identification, 100% and 100%, respectively. The results of HLA crossmatching were not reported from four participants due to poor cell viability. Further improvements of the specimen delivery process, grading criteria for crossmatching, and format of participant summary are warranted.
Cell Survival ; Histocompatibility Testing ; Histocompatibility ; HLA-B27 Antigen ; Humans ; Leukocytes ; Mass Screening ; Suspensions

Ankylosing spondylitis (AS) is a chronic autoinflammatory disease that affects the spine and sacroiliac joints. Regarding its etiology, although HLA-B27 is known to be the strongest genetic factor of AS, much evidence suggests the potential contribution of non-MHC genes to the susceptibility to AS. Most of these non-MHC genes have been discovered in non-Asian populations; however, just some of them have been validated in Koreans. In this study, we aimed to identify additional AS-associated single-nucleotide polymorphism (SNP) candidates by replicating the candidate SNPs in Korean AS patients and healthy controls. For this, we selected three SNPs (rs11249215 in RUNX3, rs6556416 in IL12B, and rs8070463 in TBKBP1), which were previously reported as risk factors of AS but have not been studied in Koreans, and performed genotyping assays using a total of 1138 Korean samples (572 AS patients and 566 healthy controls). Of the three SNP candidates, one SNP in RUNX3 (rs11249215) was significantly associated with the risk of AS (odds ratio, 1.31; 95% confidence interval, 1.02 to 1.68, p = 0.03). These results will be helpful in elucidating the pathogenesis of AS and may be useful for developing AS risk prediction models in Koreans.
HLA-B27 Antigen ; Humans ; Polymorphism, Single Nucleotide ; Risk Factors ; Sacroiliac Joint ; Spine ; Spondylitis, Ankylosing*

Recurrent macrophage activation syndrome (MAS) is very rare. We present the case of an adolescent boy with human leukocyte antigen (HLA) B27-positive ankylosing spondylitis (AS), who experienced episodes of recurrent MAS since he was a toddler. A 16-year-old boy was admitted because of remittent fever with pancytopenia and splenomegaly after surgical intervention for an intractable perianal abscess. He had been diagnosed with hemophagocytic lymphohistiocytosis (HLH) 4 different times, which was well controlled with intravenous immunoglobulin and steroids since the age of 3. We were unable to identify the cause for the HLH. He remained symptom-free until the development of back pain and right ankle joint pain with swelling at 15 years of age. He was diagnosed with HLA B27-positive AS with bilateral active sacroiliitis. He showed symptom aggravation despite taking naproxen and methotrexate, and the symptoms improved with etanercept. On admission, his laboratory data showed leukopenia with high ferritin and triglyceride levels. Bone marrow biopsy examination showed histiocytic hyperplasia with hemophagocytosis. There was no evidence of infection. He received naproxen alone, and his symptoms and laboratory data improved without any other immunomodulatory medications. Genetic study revealed no primary HLH or inflammasome abnormalities. In this case, underlying autoimmune disease should have been considered as the cause of recurrent MAS in the young patient once primary HLH was excluded.
Abscess ; Adolescent* ; Ankle Joint ; Autoimmune Diseases ; Back Pain ; Biopsy ; Bone Marrow ; Etanercept ; Ferritins ; HLA-B27 Antigen ; Humans ; Hyperplasia ; Immunoglobulins ; Inflammasomes ; Leukocytes ; Leukopenia ; Lymphohistiocytosis, Hemophagocytic ; Macrophage Activation Syndrome* ; Macrophage Activation* ; Macrophages* ; Malaria ; Male* ; Methotrexate ; Naproxen ; Pancytopenia ; Sacroiliitis ; Splenomegaly ; Spondylitis, Ankylosing* ; Steroids ; Triglycerides

OBJECTIVE: We examined the clinical relationship between human leukocyte antigen B27 (HLA-B27) and juvenile idiopathic arthritis (JIA). Additionally, we assessed the usefulness of the Assessment of SpondyloArthritis International Society (ASAS) criteria for diagnosing juvenile spondyloarthropathies (SpA). METHODS: We retrospectively reviewed medical records of 239 patients with JIA classified according to the International League of Associations for Rheumatology (ILAR) classification to analyze the features of the joint involvement site. Results were correlated with the presence of HLA-B27. After that, we classified the 239 JIA patients according to the ASAS criteria to diagnose juvenile SpA. The relationship between the ASAS criteria and a diagnosis of juvenile SpA was analyzed by a chi-squared test. RESULTS: Back pain was associated with HLA-B27 in boys (p=0.002) but not in girls (p=0.616). In both sexes, involvement of the small joints in the lower extremities was highly associated with HLA-B27 (p=0.001 for boys, p=0.021 for girls). In addition, HLA-B27 was associated with enthesitis (p=0.004 for boys, p=0.021 for girls). Eighty-seven (36.4%) patients with JIA fulfilled the ASAS criteria; 2 (0.8%) had axial SpA and 85 (35.6%) had peripheral SpA. HLA-B27 was the most significant factor for diagnosing juvenile SpA (sensitivity 80%, specificity 99.31%, positive likelihood ratio, 116). CONCLUSION: The ILAR criteria have some weaknesses for diagnosing HLA-B27-positive JIA patients in early stages. The use of the ASAS criteria for juvenile patients will enable pediatric rheumatologists to diagnose juvenile SpA patients earlier.
Arthritis, Juvenile* ; Back Pain ; Classification* ; Diagnosis ; Female ; HLA-B27 Antigen ; Humans* ; Joints ; Leukocytes* ; Lower Extremity ; Medical Records ; Retrospective Studies ; Rheumatology ; Sensitivity and Specificity ; Spondylarthropathies* ; Spondylitis, Ankylosing

Clustered occurrences of ankylosing spondylitis (AS) in family have been noticed. We evaluated patients with AS confirmed by the modified New York criteria for familial history of AS (one or more first to third degree relatives). The clinical characteristics and the recurrence risks (number of AS patients/number of familial members) of the familial AS compared to sporadic AS were investigated. Out of a total of 204 AS patients, 38 patients (18.6%) reported that they had a familial history of AS. The recurrence risks in the familial AS patients for first, second and third degree family members were 14.5%, 5.2%, and 4.4% respectively. Erythrocyte sedimentation rate (ESR) (22.6+/-22.2 vs 35.4+/-34.4, P=0.029) and C-reactive protein (CRP) (1.24+/-1.7 vs 2.43+/-3.3, P=0.003) at diagnosis, body mass index (21.9+/-2.7 vs 23.7+/-3.3, P=0.002) and frequency of oligoarthritis (13.2% vs 33.7%, P=0.021) were significantly lower in the familial form. The presence of HLA-B27 (97.4% vs 83.1%, P=0.044) was significantly higher in familial AS. In conclusion, Korean familial AS patients show a lower frequency of oligoarthritis, lower BMI, lower ESR and CRP at diagnosis and higher presence of HLA-B27.
Adult ; Age Factors ; Arthritis, Juvenile/diagnosis/epidemiology ; Blood Sedimentation ; Body Mass Index ; C-Reactive Protein/analysis ; Demography ; Family ; Female ; HLA-B27 Antigen/metabolism ; Humans ; Interviews as Topic ; Male ; Middle Aged ; Phenotype ; Recurrence ; Republic of Korea ; Risk Factors ; Severity of Illness Index ; Sex Factors ; Spondylitis, Ankylosing/*diagnosis

PURPOSE: Intravitreal injection of bevacizumab (Avastin(R)) can lead to several intraocular complications including endophthalmitis, hemorrhage and inflammation. We present one case of acute anterior uveitis with hypopyon in an HLA-B27(+) patient following intravitreal injection of bevacizumab. CASE SUMMARY: A 40-year-old male with known central retinal vein occlusion presented with redness and decreased visual acuity in the left eye. Symptoms had developed 4 days earlier after the sixth intravitreal injection of bevacizumab in that eye. The patient had a marked anterior chamber reaction with hypopyon and posterior synechiae. Nine days after onset, similar symptoms in the left eye occurred in the uninjected right eye. Through examination and clinical manifestations, we diagnosed acute anterior uveitis associated with HLA-B27 positivity. The patient was treated with 1% prednisolone acetate, 0.5% moxifloxacin and 1% atropine in both eyes and all symptoms had resolved after 6 weeks.
Adult ; Anterior Chamber ; Atropine ; Endophthalmitis ; Hemorrhage ; HLA-B27 Antigen* ; Humans ; Inflammation ; Intravitreal Injections* ; Male ; Prednisolone ; Retinal Vein ; Uveitis, Anterior* ; Visual Acuity ; Bevacizumab

BACKGROUND: Flow cytometry (FC) HLA-B27 typing is still used extensively for the diagnosis of spondyloarthropathies. If patient blood samples are stored for a prolonged duration, this testing can be performed in a batch manner, and in-house cellular controls could easily be procured. In this study, we investigated various methods of storing patient blood samples. METHODS: We compared four storage methods: three methods of analyzing lymphocytes (whole blood stored at room temperature, frozen mononuclear cells, and frozen white blood cells [WBCs] after lysing red blood cells [RBCs]), and one method using frozen platelets (FPLT). We used three ratios associated with mean fluorescence intensities (MFI) for HLAB27 assignment: the B27 MFI ratio (sample/control) for HLA-B27 fluorescein-5-isothiocyanate (FITC); the B7 MFI ratio for HLA-B7 phycoerythrin (PE); and the ratio of these two ratios, B7/B27 ratio. RESULTS: Comparing the B27 MFI ratios of each storage method for the HLA-B27+ samples and the B7/B27 ratios for the HLA-B7+ samples revealed that FPLT was the best of the four methods. FPLT had a sensitivity of 100% and a specificity of 99.3% for HLA-B27 assignment in DNA-typed samples (N=164) when the two criteria, namely, B27 MFI ratio >4.0 and B7/B27 ratio <1.5, were used. CONCLUSIONS: The FPLT method was found to offer a simple, economical, and accurate method of FC HLA-B27 typing by using stored patient samples. If stored samples are used, this method has the potential to replace the standard FC typing method when used in combination with a complementary DNA-based method.
Blood Platelets/metabolism ; Erythrocytes/metabolism ; *Flow Cytometry ; Freezing ; HLA-B27 Antigen/*blood ; HLA-B7 Antigen/blood ; Histocompatibility Testing ; Humans ; Leukocytes, Mononuclear/metabolism ; Real-Time Polymerase Chain Reaction ; Spondylarthropathies/diagnosis ; Temperature

BACKGROUND: Flow cytometry (FC) HLA-B27 typing is still used extensively for the diagnosis of spondyloarthropathies. If patient blood samples are stored for a prolonged duration, this testing can be performed in a batch manner, and in-house cellular controls could easily be procured. In this study, we investigated various methods of storing patient blood samples. METHODS: We compared four storage methods: three methods of analyzing lymphocytes (whole blood stored at room temperature, frozen mononuclear cells, and frozen white blood cells [WBCs] after lysing red blood cells [RBCs]), and one method using frozen platelets (FPLT). We used three ratios associated with mean fluorescence intensities (MFI) for HLAB27 assignment: the B27 MFI ratio (sample/control) for HLA-B27 fluorescein-5-isothiocyanate (FITC); the B7 MFI ratio for HLA-B7 phycoerythrin (PE); and the ratio of these two ratios, B7/B27 ratio. RESULTS: Comparing the B27 MFI ratios of each storage method for the HLA-B27+ samples and the B7/B27 ratios for the HLA-B7+ samples revealed that FPLT was the best of the four methods. FPLT had a sensitivity of 100% and a specificity of 99.3% for HLA-B27 assignment in DNA-typed samples (N=164) when the two criteria, namely, B27 MFI ratio >4.0 and B7/B27 ratio <1.5, were used. CONCLUSIONS: The FPLT method was found to offer a simple, economical, and accurate method of FC HLA-B27 typing by using stored patient samples. If stored samples are used, this method has the potential to replace the standard FC typing method when used in combination with a complementary DNA-based method.
Blood Platelets/metabolism ; Erythrocytes/metabolism ; *Flow Cytometry ; Freezing ; HLA-B27 Antigen/*blood ; HLA-B7 Antigen/blood ; Histocompatibility Testing ; Humans ; Leukocytes, Mononuclear/metabolism ; Real-Time Polymerase Chain Reaction ; Spondylarthropathies/diagnosis ; Temperature

Reactive arthritis (ReA) is an inflammatory joint disease following genitourinary or gastrointestinal bacterial infection, most commonly by Chlamydia trachomatis. It is characterized by the inflammation in the large joints of lower extremities such as ankles and knees and sometimes accompanied by enthesitis (Achilles tendinitis, plantar fasciitis) and sacroiliitis, which made it classified as spondyloarthritis. Although there are various theories about the role of persistent bacterial infection, toll-like receptor, and human leukocyte antigen-B27 in the pathogenesis of ReA, many things are still unknown. Clinical studies about the ReA have not been done well due to the absence of widely recognized diagnostic criteria. Although the evidence of prior infection is necessary for the diagnosis, it is not uncommon that preceding infection is asymptomatic, which make it difficult to diagnose ReA. Therefore, it is necessary to consider ReA in patients suffering from inflammation in the joints of lower extremities with unknown cause. Nonsteroidal anti-inflammatory drugs, corticosteroid, and sulfasalazine have been used in the treatment of ReA but antibiotics don't seem to work. Regarding the therapeutic role of anti-tumor necrosis factor agents, there are some controversies.
Adrenal Cortex Hormones ; Animals ; Ankle ; Anti-Bacterial Agents ; Arthritis, Reactive ; Bacterial Infections ; Chlamydia trachomatis ; HLA-B27 Antigen ; Humans ; Inflammation ; Joint Diseases ; Joints ; Knee ; Lower Extremity ; Sacroiliitis ; Sulfasalazine ; Tendinopathy ; Toll-Like Receptors

Ankylosing spondylitis (AS) is the main disease entity within spondyloarthritides. AS patients can present with both articular and extra-articular manifestations. Especially, inflammatory back pain has been recognized as the main symptom of AS, however it should be noted that mechanical back pain could also ensue in advanced cases. Peripheral arthritis mostly involves in lower extremities in the form of asymmetric oligoarthritis. Enthesitis could develop in the heel, iliac crest, anterior tibial tuberosity, or anterior chest wall. As for imaging, plain radiographs are used to assess the presence or degree of sacroiliac joint and spinal involvement. Magnetic resonance imaging (MRI) is useful in detecting non-radiographic sacroiliitis, for its ability to delineate bone marrow edema. In this regard, MRI has recently been incorporated as a modality to help diagnose axial spondyloarthritis (2010 ASAS classification). Early diagnosis of AS should be based on the combination of clinical, laboratory, and imaging findings, not on solely structural changes.
Arthritis ; Back Pain ; Bone Marrow ; Early Diagnosis ; Edema ; Heel ; HLA-B27 Antigen ; Humans ; Lower Extremity ; Magnetic Resonance Imaging ; Sacroiliac Joint ; Sacroiliitis ; Spondylitis, Ankylosing ; Thoracic Wall