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1.
Sci Rep ; 9(1): 14552, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31601947

RESUMO

Although several risk factors exist for acute coronary syndrome (ACS) no biomarkers for survival or risk of re-infarction have been validated. Previously, reduced serum concentrations of anti-ß1AR Ab have been implicated in poorer ACS outcomes. This study further evaluates the prognostic implications of anti-ß1AR-Ab levels at the time of ACS onset. Serum anti-ß1AR Ab concentrations were measured in randomly selected patients from within the PLATO cohort. Stratification was performed according to ACS event: ST-elevation myocardial infarct (STEMI) vs. non-ST elevation myocardial infarct (NSTEMI). Antibody concentrations at ACS presentation were compared to 12-month all-cause and cardiovascular mortality, as well as 12-month re-infarction. Sub-analysis, stratifying for age and the correlation between antibody concentration and conventional cardiac risk-factors was subsequently performed. Serum anti-ß1AR Ab concentrations were measured in 400/799 (50%) STEMI patients and 399 NSTEMI patients. Increasing anti-ß1AR Ab concentrations were associated with STEMI (p = 0.001). Across all ACS patients, no associations between anti-ß1AR Ab concentration and either all-cause cardiovascular death or myocardial re-infarction (p = 0.14) were evident. However among STEMI patients ≤60 years with anti-ß1AR Ab concentration median (14/198 (7.1%) vs. 2/190 (1.1%)); p = 0.01). Similarly, the same sub-group demonstrated greater risk of cardiovascular death in year 1, including re-infarction and stroke (22/198 (11.1%) vs. 10/190 (5.3%); p = 0.017). ACS Patients ≤60 years, exhibiting lower concentrations of ß1AR Ab carry a greater risk for early re-infarction and cardiovascular death. Large, prospective studies quantitatively assessing the prognostic relevance of Anti-ß1AR Ab levels should be considered.

2.
Front Immunol ; 10: 1600, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354737

RESUMO

Objective: Sjögren's syndrome is a heterogeneous inflammatory disorder frequently involving peripheral nerves with a wide spectrum of sensory modalities and distribution patterns. The objective of this cross-sectional study was to determine characteristics of Sjögren's syndrome as a cause for severe neuropathy with limb weakness. Methods: One hundred and eighty four patients with polyneuropathy associated with limb weakness underwent routine diagnostics including investigations for Sjögren's syndrome. Forty-four patients with Sjögren's syndrome (ACR-EULAR classification criteria) and severe neuropathy were identified. Results: Sjögren's syndrome was found at a median age of 63 years and the gender distribution showed a balanced female-male ratio of 1:1. Anti-SSA(Ro) antibodies were detected in 48% while seronegative patients were diagnosed with Sjögren's syndrome based on sialadenitis on minor salivary gland biopsy with a focus score ≥1. The majority of patients (93%) were diagnosed with Sjögren's syndrome after neurological symptoms appeared. Limbs were symmetrically involved in 84% of patients (57% tetraparesis, 27% paraparesis). Sensory function was not affected in 11% of patients indicating that Sjögren's syndrome associated neuropathy can present as a pure motor syndrome. Electrophysiological measurements did not reveal pathognomonic findings (23% demyelinating pattern, 36% axonal pattern, 41% both demyelinating and axonal damage signs). More than half of our patients fulfilled the European Federation of Neurological Societies (EFNS) diagnostic criteria for CIDP indicating that distinction between Neuro-Sjögren and other causes of neuropathy such as CIDP is challenging. Interpretation: Our findings show that severe neuropathy with limb weakness is often associated with Sjögren's syndrome. This is of great importance in identifying and understanding the causes of immune mediated polyneuropathy.

3.
Dtsch Med Wochenschr ; 144(11): 748-752, 2019 06.
Artigo em Alemão | MEDLINE | ID: mdl-31163474

RESUMO

In Germany, baricitinib and tofacitinib have been approved for the treatment of at least moderately active rheumatoid arthritis after the failure of conventional disease modifying anti-rheumatic drugs in 2017, and tofacitinib also for psoriatic arthritis and ulcerative colitis. Both baricitinib and tofacitinib can be taken orally and reversibly inhibit Janus kinases (JAK) and therefore the signaling of a large number of cytokines via the JAK/STAT pathway. JAK inhibitors have been shown to be at least as efficacious in rheumatoid arthritis as adalimumab and tofacitinib was also efficacious in psoriatic arthritis. Since they inhibit many cytokines, it is likely that in the future they will be applied for the treatment of further chronic inflammatory disorder such as connective tissue diseases and vasculitis. The adverse events of JAK inhibitors are comparable to those observed with biologicals, only herpes zoster is slightly more common. In the placebo-controlled trials, venous thromboembolic events (VTE) were more common in the baricitinib treated patients. The VTE rate does not appear to be elevated in baricitinib treated patients compared to RA cohorts however.In conclusion, JAK inhibitors are a powerful new treatment of RA and likely many other rheumatic diseases and fulfill an unmet need since they may be taken orally.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Inibidores de Janus Quinases/uso terapêutico , Azetidinas/uso terapêutico , Alemanha , Humanos , Piperidinas/uso terapêutico , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Sulfonamidas/uso terapêutico
4.
Clin Exp Rheumatol ; 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31140396

RESUMO

OBJECTIVES: Spondyloarthritis (SpA) is a chronic inflammatory disease of unknown aetiology. Previously, we identified autoantibodies against CD74 in sera of SpA patients. The aim of this study was to evaluate CD74 as a T cell antigen in SpA. METHODS: Recombinant CD74 protein and a panel of selected peptides representing its amino acid residues were examined for their capability to stimulate peripheral blood mononuclear cells from patients with SpA. In particular, cytokine production by CD4+ T cells was evaluated with flow cytometric detection of intracellular TNF-α, IFNγ, TGFß and IL-17A. Patients' sera were tested for antibodies against CD74 using ELISA. Samples from patients with rheumatoid arthritis and healthy blood donors were similarly tested as controls. RESULTS: Significantly more CD4+ T cells from SpA patients produced TNF-α, IFNγ and IL-17A in response to recombinant CD74 than patients with rheumatoid arthritis or healthy blood donors. Among evaluated epitopes, the most promiscuous one lies within the peptide of the amino acid residues 142-185, which appeared more immunogenic. Further, the proportion of cytokine producing CD4+ T cells was significantly higher among SpA patients with autoantibodies against CD74. CONCLUSIONS: CD74 is a T cell antigen in SpA, eliciting Th1 and Th17 responses, which may be relevant in disease pathogenesis. Recognition of the highly immunogenic amino acid residues of CD74 may contribute to our understanding of autoimmune responses of T helper cells in SpA.

5.
Z Rheumatol ; 78(6): 511-517, 2019 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-30937527

RESUMO

The prevalence of primary Sjögren's syndrome (pSS) is between 1:100 and 1:1000 and it is therefore the most common connective tissue disease. Nevertheless, it can be difficult to diagnose pSS as the symptoms are frequently unspecific and diagnostic markers are lacking in many patients. In addition, only few controlled therapeutic studies of pSS have been carried out so that the optimal management is not yet clear. Meanwhile, outcome parameters to monitor clinical improvement have been developed and a large number of therapeutic studies are currently being performed. This review article summarizes the current diagnostic and treatment options for pSS.


Assuntos
Síndrome de Sjogren , Humanos , Prevalência , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologia , Síndrome de Sjogren/terapia
6.
Dtsch Med Wochenschr ; 144(9): 595-600, 2019 05.
Artigo em Alemão | MEDLINE | ID: mdl-31026868

RESUMO

To prevent serious complications such as permanent loss of vision and structural vascular damage, treatment must be initiated quickly in patients with giant-cell arteritis (GCA). So far, usually long-term corticosteroids in cumulative high dosages have been the standard therapy option. However, steroids are often insufficient to achieve adequate disease control and are associated with serious adverse events. Therefore, steroid-sparing therapy options are the focus of interest.


Assuntos
Arterite de Células Gigantes/tratamento farmacológico , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos
7.
Front Immunol ; 10: 574, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30972069

RESUMO

Axial spondyloarthritis (axSpA) is often diagnosed late due to the non-specific nature of its main symptom [chronic back pain (CBP)] and to the paucity of diagnostic markers, particularly in regions with low HLA-B27 prevalence, such as the Middle-East. We tested the performance of IgG4 and IgA anti-CD74 antibodies as an early diagnostic marker for axSpA, compared with the performance of HLA-B27, in Lebanon. Sera of axSpA patients diagnosed by the rheumatologist and also fulfilling the imaging arm of the ASAS criteria (patients) and of blood donors (BD) (controls) were analyzed for HLA-B27, IgG4 and IgA anti-CD74, blinded to clinical characteristics. Receiver Operating Characteristic curves were constructed to identify an optimal cut-off point for anti-CD74 antibodies. Diagnostic properties were calculated (sensitivity, specificity, positive, and positive predictive values (PPV, NPV), Likelihood ratios) for each marker. Forty-nine axSpA patients and 102 BD were included in the final analysis. IgA anti-CD74 correlated poorly with axSpA (Area Under the Curve (AUC) 0.657), whereas IgG4 anti-CD74 had a good discriminative value (AUC 0.837). Respectively, for HLA-B27, IgG4 anti-CD74, and the combination of both, we found a sensitivity of 33-92-33%, specificity of 96-79-98%, PPV 80-68-89%, NPV 75-95-75%, and LR+ 8.2-4.4-16.5. IgG4 anti-CD 74 were positive in 88% of HLA-B27 negative axSpA patients, and correlated with BASDAI. In this first study in a population with low HLA-B27 prevalence, IgG4 anti-CD74 antibodies combined with HLA-B27 showed higher diagnostic value than HLA-B27 alone for early axSpA. IgG4 anti-CD74 should be considered for further evaluation as an early axSpA diagnostic marker in future dedicated research, particularly in patients with CBP.

8.
Int J Rheum Dis ; 22(4): 708-714, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30729696

RESUMO

AIM: To calculate the prevalence of human leukocyte antigen (HLA)-B27 in axial spondyloarthritis patients (axSpA) compared to blood donors (BD) in Lebanon, to identify the clinical and radiological findings associated with HLA-B27 and to estimate the proportion of patients fulfilling the clinical arm of the Assessment of the Spondyloarthritis International Association (ASAS) criteria. METHOD: Consecutive Lebanese adult axSpA patients fulfilling the ASAS classification criteria were included from 12 rheumatology clinics across Lebanon. BD served as controls. A binary logistic regression was used to study the association between HLA-B27 and the disease features. RESULTS: A total of 247 individuals were included (141 axSpA patients and 106 BD). The prevalence of HLA-B27 was 3.8% in BD and 41.1% in axSpA. Overall, 39.7% of the axSpA patients fulfilled the clinical arm of the ASAS classification criteria. Sensitivity of HLA-B27 for axSpA was 41.1%, specificity was 96.2%, positive predictive value was 93.6%, and negative predictive value was 55.13%. Positive likelihood ratio (LR) was 10.9 and negative LR was 1.63. We found a positive association of HLA-B27 with family history of SpA and psoriasis. CONCLUSION: Our study confirmed a low prevalence of HLA-B27 in axSpA patients and BD in this Lebanese population, However, we found a high specificity and positive LR, as well as the same number of axSpA patients fulfilling the clinical arm of the ASAS criteria as in European studies. HLA-B27 is therefore valuable for identification of axSpA in Lebanese patients despite the overall low prevalence in this population. Our results may guide future evaluations the role of HLA-B27 in planning local referral strategies.


Assuntos
Doadores de Sangue , Frequência do Gene , Antígeno HLA-B27/genética , Espondilartrite/genética , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Antígeno HLA-B27/imunologia , Humanos , Líbano/epidemiologia , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Fenótipo , Prevalência , Fatores de Risco , Espondilartrite/diagnóstico , Espondilartrite/epidemiologia , Espondilartrite/imunologia , Adulto Jovem
9.
Dtsch Med Wochenschr ; 143(24): 1778-1782, 2018 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-30508859

RESUMO

Primary Sjögren's syndrome (pSS) is an autoimmune disease affecting the salivary and lachrymal glands. The patients complain of symptoms of dry eyes and dry mouth, but up to 50 % may additionally develop extraglandular manifestations such as arthritis, vasculitis, polyneuropathy, pulmonary fibrosis or interstitial nephritis. Most therapeutic studies on the glandular manifestations of pSS failed to meet their primary endpoints, possibly since many of the patients had already advanced and irreversible disease.In recent years several important advances have been made. The role of B and T lymphocytes in the pathogenesis of pSS has been identified. The disease activity scores ESSDAI and ESSPRI were developed and can now be used as endpoints in therapeutical studies. Since then, numerous promising new drugs, mostly affecting B and T lymphocytes, have been studied in clinical trials. New classification criteria have been proposed, which will be an important tool in making a diagnosis in an early disease stage, in which the glandular function may still be normal. It is very likely therefore, that we will soon have efficient therapies, which will be able to stop the disease progression in an early stage of pSS.

10.
Int J Mol Sci ; 19(12)2018 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-30501024

RESUMO

The latest revision of the McDonald criteria of 2017 considers the evidence of an intrathecal immunoglobulin (IgG) synthesis as a diagnostic criterion for dissemination in time in multiple sclerosis. While the detection of oligoclonal bands is considered as the gold standard, determination of kappa free light chains might be a promising tool as a less technically demanding and cost saving method. However, data on the direct comparison between kappa free light chains and oligoclonal bands are limited and no study to date has used the highly sensitive method of polyacrylamide gels with consecutive silver staining for the demonstration of oligoclonal bands. Furthermore, the impact of the revised McDonald criteria of 2017 on the role of kappa free light chains as a biomarker has not been investigated. Nephelometry was used to determine kappa free light chains in cerebrospinal fluid (CSF) and serum from 149 patients with their first demyelinating event between 2010 and 2015. Clinical data, kappa free light chains, and oligoclonal band status were compared at the time of initial diagnosis and after follow-up to identify converters from clinically isolated syndrome to multiple sclerosis. An elevated kappa free light chain index (>5.9) was found in 79/83 patients (95%) with multiple sclerosis diagnosed at baseline, slightly less frequent than oligoclonal bands (98.8%). 18/25 (72%) patients who converted from clinically isolated syndrome to multiple sclerosis showed an elevated kappa free light chain index compared to 20/25 (80%) patients with positive oligoclonal bands. In patients with stable clinically isolated syndrome 7/41 (17%) displayed an elevated kappa free light chain index against 11/41 (27%) oligoclonal band positive patients. Only two patients with stable clinically isolated syndrome showed an elevated kappa free light chain index but were oligoclonal bands negative. In conclusion, determination of the kappa free light chain index is a promising diagnostic approach to assess intrathecal immunoglobulin synthesis in multiple sclerosis. Nevertheless, oligoclonal bands are highly prevalent in multiple sclerosis and can detect an intrathecal synthesis of IgG even when the kappa free light chain index is below the threshold. We consider sequential use of both methods as reasonable.

11.
PLoS One ; 13(12): e0209343, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30586461

RESUMO

BACKGROUND: The TNFSF13B (TNF superfamily member 13b) gene encodes BAFF, a cytokine with a crucial role in the differentiation and activation of B cells. An insertion-deletion variant (GCTGT→A) of this gene, leading to increased levels of BAFF, has been recently implicated in the genetic predisposition to several autoimmune diseases, including multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. Based on the elevated levels of this cytokine found in patients with giant cell arteritis (GCA) and systemic sclerosis (SSc), we aimed to assess whether this functional variant also represents a novel genetic risk factor for these two disorders. METHODS: A total of 1,728 biopsy-proven GCA patients from 4 European cohorts, 4,584 SSc patients from 3 European cohorts and 5,160 ethnically-matched healthy controls were included in the study. The single nucleotide polymorphism (SNP) rs374039502, which colocalizes with the genetic variant previously implicated in autoimmunity, was genotyped using a custom TaqMan assay. First, association analysis was conducted in each independent cohort using χ2 test in Plink (v1.9). Subsequently, different case/control sets were meta-analyzed by the inverse variance method. RESULTS: No statistically significant differences were found when allele distributions were compared between cases and controls for any of the analyzed cohorts. Similarly, combined analysis of the different sets evidenced a lack of association of the rs374039502 variant with GCA (P = 0.421; OR (95% CI) = 0.92 (0.75-1.13)) and SSc (P = 0.500; OR (95% CI) = 1.05 (0.91-1.22)). The stratified analysis considering the main clinical subphenotypes of these diseases yielded similar negative results. CONCLUSION: Our data suggest that the TNFSF13B functional variant does not contribute to the genetic network underlying GCA and SSc.


Assuntos
Fator Ativador de Células B/genética , Predisposição Genética para Doença , Arterite de Células Gigantes/genética , Escleroderma Sistêmico/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Estudos de Casos e Controles , Estudos de Coortes , Europa (Continente) , Feminino , Redes Reguladoras de Genes/genética , Técnicas de Genotipagem , Arterite de Células Gigantes/patologia , Humanos , Mutação INDEL , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Escleroderma Sistêmico/patologia
12.
J Med Case Rep ; 12(1): 332, 2018 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-30400821

RESUMO

BACKGROUND: Osteoarticular tuberculosis is rare in Germany. In particular, trochanteric bursitis is an extremely rare manifestation of osteoarticular tuberculosis. We describe a case of tuberculous coxitis with trochanteric bursitis, successfully treated with a fourfold tuberculostatic therapy. CASE PRESENTATION: We report the case of a 43-year-old human immunodeficiency virus-negative Sudanese man with osteoarticular tuberculosis, who was originally admitted with the suspected diagnosis of ankylosing spondylitis. Low grade fever together with the positive result of an interferon-gamma release assay test as well as findings from magnetic resonance imaging provided clues to the diagnosis. A definitive diagnosis could be set after a computed tomography-guided biopsy. CONCLUSIONS: Apart from a rare involvement pattern of osteoarticular tuberculosis, including trochanteric bursitis, this case highlights the increasing importance of osteoarticular tuberculosis as a differential diagnosis of rheumatic disorders. With the growing migration flows from tuberculosis-endemic African countries, clinicians in central and northern Europe may be more frequently confronted with atypical involvement patterns of osteoarticular tuberculosis.

13.
Arthritis Rheumatol ; 2018 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-30418704

RESUMO

OBJECTIVES: Autoantibodies against CD74 (anti-CD74) are associated with ankylosing spondylitis. InterSpA is a multicenter study conducted to compare sensitivity and specificity of anti-CD74 and HLA-B27 in patients with non-radiographic axial spondyloarthritis (nr-axSpA). METHODS: Patients aged 18-45 years with inflammatory back pain of ≤2 years duration and clinical suspicion of axSpA were recruited. HLA-B27 genotyping and MRI of sacroiliac joints were performed in all patients. 149 patients with chronic back pain not caused by axSpA (CBP) served as controls, furthermore 50 patients with ankylosing spondylitis (AS) and 100 blood donors were analyzed. RESULTS: 100 patients with IBP received the diagnosis of axSpA by the investigators and fulfilled the ASAS criteria. Their mean age was 29 years and the mean symptom duration 12.5 months. The sensitivity of IgA and IgG anti-CD74 related to the 100 axSpA patients was 47% and 17%. The specificity, per definition, was 95.3%, respectively. The sensitivity of HLA-B27 was 81%. The positive likelihood ratios (LR+) were 10.0 (IgA anti-CD74), 3.6 (IgG anti-CD74) and 8.1 (HLA-B27). Assuming a 5% pretest probability of axSpA in CBP patients of 5%, the posttest probability after consideration of the respective positive test results was 33.3% for IgA, 15.3% for IgG antibodies against CD74 and 28.8% for HLA-B27. Combination of IgA antibodies against CD74 and HLA-B27 provides posttest probabilities of 80.2%. CONCLUSIONS: IgA anti-CD74 may be a useful tool for identifying axSpA. The diagnostic value of the test needs to be further proven in daily practice. This article is protected by copyright. All rights reserved.

14.
Internist (Berl) ; 59(12): 1249-1254, 2018 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-30276426

RESUMO

Rheumatoid arthritis (RA) is the most important chronic inflammatory joint disease with a prevalence of 1%. When untreated the disease leads to joint destruction and therefore to functional restrictions of the patients and also to increased rates of cardiovascular and malignant diseases. After the pathophysiology of rheumatoid arthritis was better understood, in the last 20 years biologics could be developed, which are directed against targets involved in the inflammatory process in RA. Since then the remission rates of RA have substantially increased. In 2017 Janus kinase (JAK) inhibitors were additionally approved for the treatment of RA in Germany. They further broaden the therapeutic options and, in contrast to biologics, are administered orally. The response rates to therapy are better the earlier the disease is diagnosed and treated. Patients in whom RA is suspected due to a new onset of polyarthritis, should therefore be promptly referred to a rheumatologist.

15.
Otol Neurotol ; 39(8): e612-e617, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30113554

RESUMO

BACKGROUND AND HYPOTHESIS: There are some known reasons for chronic dilatory Eustachian tube dysfunction (chronic D-ETD, also known as chronic obstructive tube dysfunction), for example infections, hyperplastic adenoids, or tumors. In many cases though, none of these reasons apply. The question arises whether there might be an autoimmune pathogenesis in patients with idiopathic chronic D-ETD. METHODS: The study includes 31 consecutive patients with chronic D-ETD and 92 consecutive blood donors (BD, comparative cohort). The production of antinuclear antibodies (ANA), as an indicator for autoimmune pathologies, was measured in the serum of patients and BD. RESULTS: ANA titers were significantly higher in patients with chronic D-ETD, compared with BD (p = 0.0027). The results weighted clearly toward higher ANA titers in younger patients. A comparison of ANA titers in patients and BD aged less than 40 years showed a significant difference (p = 0.0062), whereas it was not significant between patients and BD aged ≥ 40 years (p = 0.19). CONCLUSION: The significant results of elevated ANA titers in chronic D-ETD make an autoimmune pathogenesis highly probable, at least in some of the patients concerned. Further research with higher numbers of patients is needed to confirm the hypothesis of an autoimmune chronic D-ETD. A better understanding of etiology and pathogenesis of chronic D-ETD might open up new and perhaps even causal therapeutic strategies.

16.
Sci Rep ; 8(1): 8195, 2018 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-29844438

RESUMO

A rare variant (BAFF-var) of the tumor necrosis factor superfamily 13b (TNFSF13B) gene has been recently associated with multiple sclerosis (MS) and systemic lupus erythematosus (SLE). The aim of this study was to investigate the association between TNFSF13B BAFF-var and susceptibility to rheumatoid arthritis (RA) and replicate that association in SLE. 6,218 RA patients, 2,575 SLE patients and 4,403 healthy controls from three different countries were included in the study. TNFSF13B BAFF-var was genotyped using TaqMan allelic discrimination assay. PLINK software was used for statistical analyses. TNFSF13B BAFF-var was significantly associated with RA (p = 0.015, OR = 1.21, 95% CI = 1.03-1.41) in the Spanish cohort. A trend of association was observed in the Dutch (p = 0.115) and German (p = 0.228) RA cohorts. A meta-analysis of the three RA cohorts included in this study revealed a statistically significant association (p = 0.002, OR = 1.24, 95% CI = 1.10-1.38). In addition, TNFSF13B BAFF-var was significantly associated with SLE in the Spanish (p = 0.001, OR = 1.41, 95% CI = 1.14-1.74) and the German cohorts (p = 0.030, OR = 1.86, 95% CI = 1.05-3.28), with a statistically significant p-value obtained in the meta-analysis (p = 0.0002, OR = 1.46, 95% CI = 1.09-2.32). The results obtained confirm the known association of TNFSF13B BAFF-var with SLE and, for the first time, demonstrate that this variant contributes to susceptibility to RA.

17.
Arthritis Res Ther ; 20(1): 38, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29490705

RESUMO

BACKGROUND: Anti-CD74 IgG antibodies are reported to be elevated in patients with axial spondyloarthritis (axSpA). This study assessed the diagnostic value of anti-CD74 antibodies in patients with early axSpA. METHODS: Anti-CD74 IgG and IgA antibodies were first measured in an exploratory cohort of patients with radiographic axSpA (138 patients with ankylosing spondyloarthritis (AS)) and 57 healthy controls and then were measured in patients with early axSpA (n = 274) and with non-SpA chronic back pain (CBP) (n = 319), participating in the spondyloarthritis caught early (SPACE) prospective cohort study of patients under 45 years old with early back pain (for ≥ 3 months, but ≤ 2 years). RESULTS: In the exploratory cohort, anti-CD74 IgG antibodies were present in 79.7% of patients with AS vs. 43.9% of healthy controls (p < 0.001). Anti-CD74 IgA antibodies were present in 28.5% of patients with AS vs. 5.3% of healthy controls (p < 0.001). In the SPACE cohort, anti-CD74 IgG antibody levels were present in 46.4% of the patients with axSpA vs. 47.9% of the patients with CBP (p = 0.71). Anti-CD74 IgA antibodies were present in 54.7% of the patients with axSpA and 37.0% of the patients with CBP (p < 0.001). This resulted in a positive predictive value of 58.8% (compared to a prior probability of 46.2%) and a negative predictive value of 59.1% (compared to a prior probability of 53.8%). In a regression model, total serum IgA was associated with axSpA odds ratio (OR) 1.19, p < 0.001) whereas anti-CD74 IgA was not (OR) 1.01, p = 0.33). Furthermore, anti-CD74 IgA was associated with sacroiliitis on magnetic resonance imaging (MRI) (OR) = 2.50, p = 0.005) and heel enthesitis (OR) = 2.56, p = 0.002). CONCLUSIONS: Albeit anti-CD74 IgA is elevated in patients with early axSpA, this elevation is not sufficiently specific to yield significant diagnostic value in patients under 45 years old presenting with early back pain.

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