Clinical and laboratory factors associated with bamboo spine in patients with axial spondyloarthritis: are there clues for bamboo spine?

OBJECTIVES: To analyse the clinical and laboratory factors associated with bamboo spine. METHODS: Data of patients fulfilling the 2009 ASAS classification criteria for axial spondyloarthritis, registered in the national, multicentre, longitudinal, and observational database of TReasure was analysed. Radiographs were assessed using the Bath Ankylosing Spondylitis Radiologic Index (BASRI). Data of patients with a bamboo spine (Group 1) was compared to data derived from patients with a longstanding disease of at least 15 years but no syndesmophytes (Group 2). RESULTS: Out of the 5060 patients, 1246 had eligible radiographs. There were 111 patients (8.9%) with a bamboo spine. Male sex was more common among patients with bamboo spine. The median BMI of 27.7 (25.8-31.1) in Group1 was higher than the BMI of 25.9 (22.9-29.2) in Group 2 (p<0.001). Hip arthritis, present or documented by a physician, was more common in Group 1 [(58/108 (53.7%) vs. 35/103 (34%), p=0.004]. There was a tendency towards a more prevalent enthesitis in these patients [29.1% (25/86) vs. 15.9%(11/69), p=0.054]. HLA-B27 status did not differ between groups. Smoking was more prevalent in Group 1. Multivariate logistic regression analysis revealed that male sex, body mass index, hip arthritis, and enthesitis are associated with bamboo spine in axSpA. CONCLUSIONS: Bamboo spine was more common in the male sex and associated with a delay in diagnosis, high BMI, hip involvement, and enthesitis. The constellation of increased body weight, hip arthritis, and enthesitis may imply that mechanical stress contributes to radiographic damage in the presence of chronic inflammation.

Recent advances in the diagnosis and therapy of large vessel vasculitis.

Large vessel vasculitis (LVV), including Takayasu arteritis (TAK) and giant cell arteritis (GCA), causes granulomatous vascular inflammation mainly in large vessels, and is the most common primary vasculitis in adults. Vascular inflammation may evoke many clinical features including vision impairment, stroke, limb ischemia, and aortic aneurysms. The best way to diagnose LVV is to combine medical history, physical examination, various laboratory tests, and imaging modalities. Progress in imaging modalities facilitated early diagnosis and follow­up of the disease activity. Conventional angiography is no longer the gold standard for the diagnosis of TAK. Similarly, temporal artery biopsy is no longer the only tool for diagnosing cranial GCA. In selected cases, color Doppler ultrasound may be used for this purpose. Despite some similarities, TAK and GCA differ in many aspects and they are different diseases. They also have different clinical subtypes. The presence of aortitis does not always implicate the diagnosis of TAK or GCA; infectious aortitis, as well as noninfectious aortitis associated with other autoimmune rheumatic diseases should be excluded. Treatment of LVV includes glucocorticoids (GCs), conventional immunosuppressive agents, and biological drugs. Tumor necrosis factor inhibitors are ineffective in GCA but effective in TAK. On the other hand, tocilizumab may be used to treat both diseases. Promising targeted therapies evaluated in ongoing clinical trials include, for example, anti­IL­12/23 (ustekinumab), anti­IL­17 (secukinumab), anti­IL­1 (anakinra), anti­IL­23 (guselkumab), anti­cytotoxic T­lymphocyte antigen 4 (abatacept), Janus kinase inhibitors (tofacitinib and upadacitinib), anti­granulocyte / macrophage colony­stimulating factor (mavrilimumab), and endothelin receptor (bosentan) therapies.

Tuberculin skin test before biologic and targeted therapies: does the same rule apply for all?

This study aimed to compare Tuberculin Skin Test (TST) and QuantiFERON®-TB Gold In-Tube (QFT-GIT) test in rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients scheduled for biological and targeted synthetic disease modifying anti-rheumatic drugs (DMARDs) in a Bacillus Calmette-Guérin-vaccinated population. Adult RA (n = 206) and SpA (n = 392) patients from the TReasure database who had both TST and QFT-GIT prior to initiation of biological and targeted synthetic DMARDs were included in the study. Demographic and disease characteristics along with pre-biologic DMARD and steroid use were recorded. The distribution of TST and performance with respect to QFT-GIT were compared between RA and SpA groups. Pre-biologic conventional DMARD and steroid use was higher in the RA group. TST positivity rates were 44.2% in RA and 69.1% in SpA for a 5 mm cutoff (p < 0.001). Only 8.9% and 15% of the patients with RA and SpA, respectively, tested positive by QFT-GIT. The two tests poorly agreed in both groups at a TST cutoff of 5 mm and increasing the TST cutoff only slightly increased the agreement. Among age, sex, education and smoking status, pre-biologic steroid and conventional DMARD use, disease group, and QFT-GIT positivity, which were associated with a 5 mm or higher TST, only disease group (SpA) and QFT-GIT positivity remained significant in multiple logistic regression. TST positivity was more pronounced in SpA compared to that in RA and this was not explainable by pre-biologic DMARD and steroid use. The agreement of TST with QFT-GIT was poor in both groups. Using a 5 mm TST cutoff for both diseases could result in overestimating LTBI in SpA.

Physicians' Biological Drug Preference in Patients With Rheumatoid Arthritis and Spondyloarthritis With a History of Malignancy: Perspectives From the Treasure Database.

OBJECTIVE: Because of concerns about malignancy risks, using biological disease-modifying antirheumatic drugs (bDMARDs) in patients with a history of malignancy remains a challenging issue in rheumatology practice. This study aimed to investigate bDMARD preferences of physicians when treating of rheumatoid arthritis (RA) and spondyloarthritis (SpA) patients with a history of malignancy. METHODS: The data for this cross-sectional study were gathered from the TReasure database using a date range of December 2017 and January 2020. Biological disease-modifying antirheumatic drug preferences were analyzed for 40 RA patients and 25 SpA patients with a history of malignancy. RESULTS: The most frequently prescribed bDMARD was rituximab, which was given to 28 RA patients (70%). For 25 patients (62.5%), the time between the diagnosis of malignancy and starting on a bDMARD regimen was less than 60 months, with a median interval of 43.5 months. Among SpA patients, the preferred bDMARDs were secukinumab and etanercept, which were each administered to 7 patients (28%). For 13 SpA patients (52%), the time between the diagnosis of malignancy and starting on bDMARDs was less than 60 months, with a median interval of 97 months. CONCLUSIONS: The observed bDMARD preferences may be related to the therapeutic effects of rituximab on lymphoproliferative malignancies, the protective effects of secukinumab on tumor progression, and the short half-life of etanercept. Biological disease-modifying antirheumatic drugs should be used in RA and SpA patients with malignancy in case of high inflammatory activity.

Uveitis-related Factors in Patients With Spondyloarthritis: TReasure Real-Life Results.

PURPOSE: Spondyloarthritis (SpA) is a group of diseases with overlapping skeletal and extra-articular features. Acute anterior uveitis (AAU) is the most common extra-articular manifestation of SpA. The relation between AAU and SpA is well defined in the current literature. Our study aims to analyze the frequency and factors associated with AAU in different forms of SpA in a large nationwide cohort of Turkish SpA patients. DESIGN: Retrospective cohort study. METHODS: The data were obtained from the TReasure database, which compiles data from records of the web-based Rheumatoid Arthritis (RA) and SpA patients treated with biological disease-modifying anti-rheumatismal drugs from different regions of Turkey. The clinical characteristics of SpA and uveitis are recorded. RESULTS: Data of the 4,297 SpA patients were included in the study. Overall, 475 of 4,297 patients (11.0%) had experienced 1 or more episodes of uveitis. SpA patients with older age (P < .001), a smoking history (P = .004), delayed diagnosis (P = .001), longer disease duration (P < .001), arthritis (P < .001), positive HLA-B27 (P < .001), a family history of SpA (P < .001), and radiographic damage (presence of sacroiliitis, syndesmophytes, bamboo spine, hip involvement) (P < .001 for all) more commonly had uveitis. On the other hand, uveitis was less prevalent in patients with psoriasis and psoriatic arthritis (P < .001 for both). CONCLUSION: Uveitis may be the key feature leading to SpA diagnosis. Patients with radiographic damage and long disease duration have an increased risk for uveitis in both male and female SpA patients. Patients with uveitis should be referred to a rheumatologist for a thorough evaluation of SpA.

Hemophagocytic lymphohistiocytosis: a review inspired by the COVID-19 pandemic.

Hemophagocytic syndrome (HPS) or hemophagocytic lymphohistiocytosis (HLH) is an acute and rapidly progressive systemic inflammatory disorder characterized by cytopenia, excessive cytokine production, and hyperferritinemia. Common clinical manifestations of HLH are acute unremitting fever, lymphadenopathy, hepatosplenomegaly, and multiorgan failure. Due to a massive cytokine release, this clinical condition is considered as a cytokine storm syndrome. HPS has primary and acquired (secondary, reactive) forms. Its primary form is mostly seen in childhood and caused by various mutations with genetic inheritance and, therefore, is called familial HLH. Secondary HLH may be caused in the presence of an underlying disorder, that is, secondary to a malignant, infectious, or autoimmune/autoinflammatory stimulus. This paper aims to review the pathogenesis and the clinical picture of HLH, and its severe complication, the cytokine storm, with a special emphasis on the developed classification criteria sets for rheumatologists, since COVID-19 infection has clinical symptoms resembling those of the common rheumatologic conditions and possibly triggers HLH. MED-LINE/Pubmed was searched from inception to April 2020, and the following terms were used for data searching: "hemophagocytic syndrome" OR "macrophage activation syndrome" OR "hemophagocytic lymphohistiocytosis", OR "cytokine storm". Finally, AND "COVID-19" was included in this algorithm. The selection is restricted to the past 5 years and limited numbers of earlier key references were manually selected. Only full-text manuscripts, published in an English language peer-reviewed journal were included. Manuscript selection procedure and numbers are given in Fig. 2. Briefly, the database search with the following terms of "Hemophagocytic syndrome" OR "Macrophage activation syndrome" OR "Hemophagocytic lymphohistiocytosis" OR "Cytokine storm" yielded 6744 results from inception to April 2020. The selection is restricted to the past 5 years and only limited numbers of earlier key references were selected, and this algorithm resulted in 3080 manuscripts. The addition of (AND "COVID-19") resulted in 115 publications of which 47 studies, together with four sections of an online book were used in the final review. No statistical method was used. HLH is triggered by genetic conditions, infections, malignancies, autoimmune-autoinflammatory diseases, and some drugs. In COVID-19 patients, secondary HLH and cytokine storm may be responsible for unexplained progressive fever, cytopenia, ARDS, neurological and renal impairment. Differentiation between the primary and secondary forms of HLH is utterly important, since primary form of HLH requires complicated treatments such as hematopoietic stem cell transplantation. Further studies addressing the performance of HScore and other recommendations in the classification of these patients is necessary.

Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment.

COVID-19 infection has a heterogenous disease course; it may be asymptomatic or causes only mild symptoms in the majority of the cases, while immunologic complications such as macrophage activation syndrome also known as secondary hemophagocytic lymphohistiocytosis, resulting in cytokine storm syndrome and acute respiratory distress syndrome, may also occur in some patients. According to current literature, impairment of SARS-CoV-2 clearance due to genetic and viral features, lower levels of interferons, increased neutrophil extracellular traps, and increased pyroptosis and probable other unknown mechanisms create a background for severe disease course complicated by macrophage activation syndrome and cytokine storm. Various genetic mutations may also constitute a risk factor for severe disease course and occurrence of cytokine storm in COVID-19. Once, immunologic complications like cytokine storm occur, anti-viral treatment alone is not enough and should be combined with appropriate anti-inflammatory treatment. Anti-rheumatic drugs, which are tried for managing immunologic complications of COVID-19 infection, will also be discussed including chloroquine, hydroxychloroquine, JAK inhibitors, IL-6 inhibitors, IL-1 inhibitors, anti-TNF-α agents, corticosteroids, intravenous immunoglobulin (IVIG), and colchicine. Early recognition and appropriate treatment of immunologic complications will decrease the morbidity and mortality in COVID-19 infection, which requires the collaboration of infectious disease, lung, and intensive care unit specialists with other experts such as immunologists, rheumatologists, and hematologists.

Predictors and the optimal duration of sustained remission in rheumatoid arthritis.

OBJECTIVE: To determine predictors and optimal duration of sustained remission (SR) in patients with rheumatoid arthritis (RA). METHODS: A total of 428 consecutive patients with RA visiting our clinic routinely between 2012 and 2013 were evaluated. Seventy seven of these patients in DAS28 remission were enrolled and followed up for 62.2 ± 9.9 months. Patients in remission ≥ 6 months (SR) and shorter (non: N-SR) were compared in terms of demographic-clinical data and the psychosocial factors. At enrollment, 1st and 5th years, patients in DAS28, SDAI, and Boolean remission were determined. RESULTS: Sixty three patients were in SR and 14 in N-SR. Lower baseline DAS28 and HAQ scores, anti-CCP were positive predictors of SR. Although the presence of anxiety, depression, fibromyalgia, and fatigue were lower in the SR group, there was no significance. Patients in DAS28 remission (100%) at baseline reduced to 64% at 1st and 42.6% at 5th years. Patients satisfying SDAI and Boolean remission at these three visits were 49%, 44%, and 32.4% vs 41%, 28%, and 20.6%, respectively. If the duration of remission is defined as 6 months, the remission rates of SDAI at inclusion and fifth years' visits were similar but Boolean remission rates differed significantly and if it is accepted as ≥ 12 months, both the SDAI and Boolean remission rates were not different. CONCLUSION: Low DAS28 and HAQ scores at baseline, anti-CCP were positive predictors of SR. Instead of 6 months, remission duration for ≥ 12 months would probably help us to predict SR independently from the chosen criteria; Boolean or SDAI.

Association of ERAP1, IL23R and PTGER4 Polymorphisms with Radiographic Severity of Ankylosing Spondylitis.

BACKGROUND: Radiographic severity of ankylosing spondylitis (AS) shows such great variance that some patients never develop syndesmophytes throughout the entire disease span, whereas some develop bamboo spine relatively early. OBJECTIVE: To study the association between ERAP1, IL23R and PTGER4 single nucleotide polymorphisms (SNPs) and radiographic severity in AS patients. METHODS: rs27044 and rs30187 (ERAP1), rs11209032 (IL23R) and rs10440635 (PTGER4) SNPs were genotyped in 235 AS patients fulfilling the modified New York criteria. Patients were classified as mild- and severe-AS according to modified Stoke AS spinal score (mSASSS). Mild-AS is defined as having mSASSS of "0" following at least 10 years of disease duration. Severe-AS is defined as having mSASSS of >20 (patients with mild vertebral changes (i.e. squaring or erosions) were omitted for clear stratification) regardless of disease duration. RESULTS: The genotype distributions and allele frequencies of ERAP1 rs27044 and rs30187, IL23R rs11209032 and PTGER4 rs10440635 SNPs were similar in mild- (n=171, mSASSS=0, 55.6% HLA-B27 positive) and severe-AS patients (n=64, mSASSS=48.5±17.8, 73.4% HLA-B27 positive). After adjustment for clinical differences between groups (gender, disease duration, HLA-B27 and smoking status) by logistic regression analysis, none of the alleles in the investigated SNPs were found to be associated with radiographic severity of AS. CONCLUSION: In radiographically well-categorized AS patients, ERAP1 rs27044 and rs30187, IL23R rs11209032 and PTGER4 rs10440635 SNPs are not found to be associated with radiographic severity of AS.

Immune and inflammatory gene expressions are different in Behçet's disease compared to those in Familial Mediterranean Fever.

OBJECTIVE: The immune classification of Behçet's disease (BD) is still controversial. In this study, we aimed to compare the immune/inflammatory gene expressions in BD with those in familial Mediterranean fever (FMF), an autoinflammatory disorder with innate immune activation. MATERIAL AND METHODS: CD4+ T cells and CD14+ monocytes were isolated from the peripheral blood mononuclear cells of Behçet's disease patients (n=10), FMF (n=6) patients, and healthy controls (n=4) with microbeads, and then, the mRNA was isolated. The expressions of 440 genes associated with immune and inflammatory responses were studied with a focused DNA microarray using a chemiluminescent tagging system. Changes above 1.5-fold and below 0.8-fold were accepted to be significant. RESULTS: In BD patients, in the CD4+ T-lymphocyte subset, interleukin 18 receptor accessory protein (1.7-fold), IL-7 receptor (1.9-fold), and prokineticin 2 (2.5-fold) were all increased compared to those in FMF patients, whereas chemokine (C-X3-C motif ) receptor-1 (CX3CR1) (0.7-fold) and endothelial cell growth factor-1 (0.6-fold) were decreased. In the CD14+ monocyte population, the V-fos FBJ murine osteosarcoma viral oncogene homolog (1.5-fold), Interleukin-8 (IL-8) (2.1-fold), and Tumor Necrosis Factor alpha (TNF-α) (1.8-fold) were all increased, whereas the chemokine (C-C motif ) ligand 5 (CCL5) (0.6-fold), C-C chemokine receptor type 7 (0.6-fold), and CX3CR1 (0.7-fold) were decreased, again when compared to those in FMF. Compared to healthy controls in the CD4+ T-lymphocyte population, in both BD and FMF patients, pro-platelet basic protein and CD27 had elevated expression. In BD and FMF patients, 24 and 19 genes, respectively, were downregulated, with 15 overlapping genes between both disorders. In the CD14+ monocytes population, chemokine (C-C motif ) receptor-1 (CCR1) was upregulated both in BD and FMF patients compared to that in the controls, whereas CCL5 was downregulated. CONCLUSION: Immune and inflammatory gene expressions seem to be variable in both the innate (CD14+) and adaptive (CD4+) immune responses in BD and FMF patients compared to those in controls, suggesting differences in immune regulation between the two disorders.

Biomarkers in Remission According to Different Criteria in Patients with Rheumatoid Arthritis.

OBJECTIVE: Remission is the primary aim in the treatment of patients with rheumatoid arthritis (RA). In this study, we aimed to evaluate biomarker profiles of patients in remission by different criteria and compare these profiles with controls. METHODS: Serum levels of calprotectin, interleukin 6 (IL-6), type II collagen helical peptide, C-terminal crosslinking telopeptide of type I collagen generated by matrix metalloproteinases (ICTP), matrix metalloproteinase 3 (MMP-3), resistin, and leptin were measured by ELISA in 80 patients. The patients were in Disease Activity Score at 28 joints with erythrocyte sedimentation rate (DAS28-ESR) remission, and had these characteristics: female/male 54/26, mean age 51.4 ± 12.1 years, mean disease duration 11.4 ± 8.1 years, rheumatoid factor positivity 68.7% (n = 55), anticyclic citrullinated peptide positivity 60.7% (n = 48). These patients were also evaluated for the American College of Rheumatology/European League Against Rheumatism (Boolean) and Simple Disease Activity Index (SDAI) remissions. Additionally, 80 age-, sex-, and comorbidity-matched individuals without rheumatic diseases were included in the study as controls. RESULTS: At recruitment of 80 patients in DAS28 remission, 33 patients (41.2%) were found in Boolean remission and 39 patients (48.7%) were in SDAI remission. Serum MMP-3, ICTP, resistin, and IL-6 levels of the 80 patients in DAS28 remission were statistically significantly higher than the controls. Patients in Boolean and SDAI remissions had significantly higher serum ICTP, resistin, and IL-6 levels in comparison with the controls. CONCLUSION: The 3 commonly used remission criteria of RA are almost similar with regard to patients' biomarker levels. Biomarker profiles of patients may provide complementary information to clinical evaluation of remission and may help to determine the patients under the risk of progression.

Accelerated infusion rates of rituximab are well tolerated and safe in rheumatology practice: a single-centre experience.

Due to the possible risk of infusion reactions of rituximab (RTX), a slow infusion rate (total infusion time, 255 min) is suggested for rheumatological use. However, especially in oncology field, accelerated infusion of RTX is reported to be well tolerated and safe. The aim of our study was to evaluate whether accelerated infusion rates of RTX would similarly be safe and tolerable in rheumatoid arthritis (RA) patients and other off-label rheumatological indications. All patients treated with RTX for RA and other autoimmune diseases between May 2011 and January 2012 were recruited to the study. Each treatment course consisted of two RTX 1,000 mg infusions, 2 weeks apart. Total time of the infusion for the first cycle was 255 min. Second and subsequent infusions were administered over 120 min as follows: 0-30 min, 100 mg; 30-60 min, 200 mg; 60-90 min, 300 mg; and 90-120 min, 400 mg. The Clinical Trials Classification of Adverse Events (CTCAE) version 4.3 was used to categorise side effects. The study population comprised 68 patients [F/M, 59:9; mean age, 52.4 (10.6) years]: 60 with RA, 4 with systemic lupus erythematosus (SLE), 1 with non-Hodgkin's lymphoma with SLE and 3 with vasculitis. A total of 77 fast infusions were administered. Eleven patients (16.2 %) had taken a fast infusion at the first course. A total of nine patients experienced at least one AE. Seven patients had a reaction on the first infusion (infusion-related reaction (IRR)), two patients on the second infusion and one patient on both infusions. When graded from 1 to 5 according to CTCAE v. 4.3, grade 1 IRRs were observed in a total of seven patients and grade 2 IRR in three patients. In this study of fast infusions, adverse events after RTX were mostly mild and seem to be well tolerated. Faster rituximab infusion times seem to be safe and might be incorporated into routine practice.

Conventional DMARD therapy (methotrexate-sulphasalazine) may decrease the requirement of biologics in routine practice of ankylosing spondylitis patients: a real-life experience.

AIM: The effect of disease-modifying antirheumatic drugs (DMARDs) in ankylosing spondylitis (AS) is still controversial. We aimed to evaluate the efficacy of sulphasalazine (SSZ) mono- or combination therapy with methotrexate (MTX) in AS patients naive to anti-tumor necrosis factor alpha (TNFα) agents. METHODS: Patients with AS (n = 87, male : female, 46 : 41) treated with SSZ (n = 61) or SSZ + MTX (n = 26) combination and a documented 6-month follow-up were evaluated retrospectively. Disease activity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), C-reactive protein and erythrocyte sedimentation rate. Requirement for anti-TNFα therapy was assessed after 6 months. RESULTS: Mean (SD) age was 43.0 (11.0) versus 40.2 (11.1) and disease duration was 11.0 (8.6) versus 8.2 (5.2) years, in the SSZ and SSZ + MTX groups, respectively. Initially, 59% (34/61) of the patients in SSZ monotherapy and 68% (17/26) in the combination arm had BASDAI > 4. At the end of the study, BASDAI scores decreased similarly in both groups (mono: 1.4 [-7-6] versus combination: 0.7 [-3-6] P = 0.2). BASDAI was > 4 in 32.8% (20/61) of patients in the SSZ monotherapy and in 44% (11/26) in the combination arm. Only 4 (6.6%) patients in the SSZ group and 2 (7.7%) in the ombination arm were switched to anti-TNFα therapies. DISCUSSION: A significant subset of our AS patients responded to SSZ mono or SSZ + MTX combination therapies at 6 months follow-up. Using BASDAI, the requirement for biological therapies decreased by 21-24%. In AS patients, including those with axial involvement only, DMARD therapy may be a reasonable first alternative to anti-TNFα therapy and may delay the switch to biologic agents.

Monitoring Achilles enthesitis in ankylosing spondylitis during TNF-alpha antagonist therapy: an ultrasound study.

OBJECTIVE: Enthesitis is considered as the primary anatomical lesion in ankylosing spondylitis (AS). Therapeutic effects of TNF-alpha antagonist treatments for enthesitis on imaging changes are still limited to case reports or small sample-sized trials. We aimed to investigate the potential of ultrasonography (US) to detect early changes after TNF-alpha antagonist therapy of Achilles enthesis of AS patients. METHODS: Forty-three AS patients with active disease, requiring TNF-alpha antagonist therapy, were included. Physical examination was performed to detect Achilles enthesitis and/or retrocalcaneal bursitis. US of the Achilles tendon was performed bilaterally. Grey-scale (GS) and power Doppler (PD) scores on a 0-2 semi-quantitative scale and total additive scores (TS) were calculated. Follow-up US examinations were performed 2 months after the initiation of therapy. RESULTS: At baseline, 11 patients (26.2%) were symptomatic in physical examination for either Achilles enthesitis or retrocalcaneal bursitis, whereas 36 (83%) had GS US pathological findings and 10 (23.3%) had PD signal. GS score and TS decreased significantly [3.6 (3.0) vs 2.3 (2.2), P < 0.001 and 4.7 (4.9) vs 2.7 (3.3), P < 0.001, respectively], whereas the decrease in PD score was not significant after 2 months of follow-up. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), ESR and CRP levels also showed significant improvements. CONCLUSIONS: Subclinical Achilles enthesitis, detected only with GS US, is present in a subset of AS patients and a significant improvement can be demonstrated after 2 months of TNF-alpha antagonist therapy. In addition to standard outcome measures, US might be an additional useful tool to monitor therapy in SpA patients with Achilles enthesitis.

Agreement between Quantiferon-TB gold test and tuberculin skin test in the identification of latent tuberculosis infection in patients with rheumatoid arthritis and ankylosing spondylitis.

OBJECTIVE: To compare the Quantiferon-TB Gold test (QTF-G) with the tuberculin skin test (TST) for the detection of latent tuberculosis infection (LTBI) among patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS), with reevaluation of the patients treated with tumor necrosis factor-alpha (TNF-alpha) antagonists in the followup. METHODS: The study involved 140 consecutive patients, 82 with RA and 58 with AS. Thirty patients were evaluated with QTF-G for detection of LTBI before and after 6 months of TNF-alpha antagonist treatment. QTF-G was also performed on 49 healthy controls. QTF-G results were recorded as positive, negative, or indeterminate. A positive TST was defined as >or= 5 mm for RA and AS. RESULTS: The percentages of positive QTF-G were comparable in RA and AS (37% vs 32%). The rate of positive QTF-G in healthy controls (29%) was also similar to RA and AS. In contrast to QTF-G results, a high rate of TST positivity was observed in AS compared to RA (82% vs 55%; p = 0.02). The total agreement between QTF-G and TST was observed to be 61% (kappa = 0.29) in the whole group, 70% (kappa = 0.42) in RA, and 49% (kappa = 0.14) in AS. After 6 months of treatment with TNF-alpha antagonists, a high rate of QTF-G change was observed in patients with indeterminate results (23% vs 3%; p = 0.03). CONCLUSION: The comparable prevalence of LTBI among the study groups according to QTF-G supports the view that QTF-G is less susceptible to external factors than TST. Sequential testing for QTF-G in patients with indeterminate or negative results may also be helpful in discriminating LTBI better.

HLA-B27-restricted CD8+ T cell response to cartilage-derived self peptides in ankylosing spondylitis.

OBJECTIVE: Several hypotheses have been proposed to explain the strong association between HLA-B27 and ankylosing spondylitis (AS). Among these, the arthritogenic peptide theory proposes that certain B27 subtype alleles bind specific arthritogenic peptide(s) due to their unique amino acid anchor residues. Cartilage antigens have been discussed as candidate targets for the immune response in AS. The recognition of HLA-B27-peptide complexes by self-reactive CD8+ T cells might contribute to joint-specific tissue damage. Therefore, we investigated the presence of autoreactive CD8+ T cells specific for cartilage-derived peptides in patients with AS. METHODS: An HLA-B27-binding prediction program and a proteasome-cutting prediction program for the human 20S proteasome were used to screen 18 human cartilage proteins for potentially immunogenic nonamer peptides. The peptides identified were used to stimulate peripheral blood mononuclear cells from 20 HLA-B27-positive patients with AS and synovial fluid (SF) mononuclear cells from 7 HLA-B27-positive patients with AS. Activation of T cells was measured by antigen-specific intracellular cytokine staining and quantified by flow cytometry. RESULTS: From the screening analysis, we identified 121 nonamer peptides. Of these, 1 peptide derived from type II collagen and 1 from type VI collagen were stimulatory for peripheral blood CD8+ T cells in only 1 of 20 patients. However, in 4 of 7 SF samples the same type VI collagen-derived nonamer peptide stimulated SF CD8+ T cells, but none of the other peptides was stimulatory. This CD8+ T cell response could be blocked by an anti-HLA-B27 antibody, confirming an HLA-B27-restricted immune response. CONCLUSION: Our findings suggest that cartilage-directed cellular autoimmunity might play an important role in joint-specific tissue damage in patients with AS. Future research is necessary to determine whether the identified peptide is of pathogenetic relevance.