Candidate autoantibodies for primary Sjögren's syndrome: where are they now?

Although ANA, SSA and SSB antibody testing are universally accepted biomarkers for Sjögren's syndrome (SS) diagnosis, they do not occur in all patients. Up to 18% of SS patients are seronegative, with potential for delayed or missed diagnosis. There are no clinically available autoantibodies with predictive value for SS end-organ complications. Over the last three decades, novel autoantibodies for SS diagnosis and monitoring have been identified but few have transitioned from research studies to clinical use. We performed a literature review of candidate serum autoantibodies to examine their persistence in the literature and potential clinical utility. Of the nineteen autoantibodies we identified, AQP5, SP-1, CA6, and PSP Abs have the most promise. Larger cohort studies are needed to determine their potential contribution in SS management.

The diagnostic accuracy of temporal artery ultrasound and temporal artery biopsy in giant cell arteritis: A single center Australian experience over 10 years.

AIM: To assess the diagnostic accuracy of temporal artery ultrasound compared with temporal artery biopsy and clinical diagnosis in patients with suspected giant cell arteritis (GCA) over 10 years in an Australian center. METHOD: Patients presenting to Westmead Hospital with possible GCA from March 2011 to December 2020 were retrospectively identified. The following parameters were obtained from the medical record: clinical presentation, inflammatory markers, temporal artery ultrasound findings, and temporal artery biopsy report. Data were assembled in a 2 × 2 table; sensitivity and specificity of temporal artery ultrasound compared with temporal artery biopsy and clinical diagnosis were calculated. RESULTS: Over the 10-year study period, 65 temporal artery ultrasounds were performed in 63 patients (n = 65; 61.9% female) with a mean ± standard deviation age of 69.6 ± 12.3 years. Thirteen out of 65 (20%) temporal artery ultrasounds had findings suggestive of GCA. Twenty patients (31.7%) had a clinical diagnosis of GCA irrespective of sonographic or biopsy findings. Compared with temporal artery biopsy, temporal artery ultrasound had a sensitivity of 71.4% and specificity of 93.3%. Compared with clinical diagnosis made by the treating rheumatologist, temporal artery ultrasound had a sensitivity of 55% and specificity of 95.3%. CONCLUSION: Temporal artery ultrasound is a useful non-invasive investigation in the assessment of suspected GCA. If positive in the setting of a suggestive clinical presentation, a temporal artery ultrasound probably avoids the need for a temporal artery biopsy. Temporal artery ultrasound could be more widely used in the clinical management of GCA.

Concordance between myositis autoantibodies and anti-nuclear antibody patterns in a real-world, Australian cohort.

OBJECTIVES: Myositis autoantibodies (MAs) were traditionally used as a diagnostic biomarker for idiopathic inflammatory myopathy (IIM). Its clinical utility had recently expanded to include interstitial lung disease (ILD) diagnosis. Depending on the patient cohort, MAs false positives can be common. Correlation between ANA indirect immunofluorescent (IIF) pattern and MAs may improve its positive predictive value (PPV). The aim of our study was to determine the PPV of MAs in IIM and ILD in a real-world patient cohort. We also assessed whether concordance between MAs and ANA IIF pattern can improve the PPV of positive MA results. METHODS: Patients with positive MAs and corresponding ANA IIF pattern were identified from Sutherland Centre of Immunology, New South Wales Health Pathology, Australia. The corresponding health records were reviewed to identify each patient's primary diagnosis. χ2 test was used to compare the PPV between MA-ANA concordant and discordant groups. RESULTS: Between January 2016 and July 2019, 118 patients were positive for at least one MA (mean age 66.7 years, 55% female). The most frequently detected autoantibodies were Ro52, anti-synthetase antibodies and PM-Scl. The PPV of MAs for IIM or ILD was 47.4%. The overall concordance rate of MAs and ANA IIF pattern was 70.2%. Patients with concordant MA-ANA results were more likely to have true clinical disease (64.1% vs 17.8%, P <0.001). CONCLUSION: Myositis autoantibodies have a low PPV for IIM and ILD in a real-world patient cohort. A positive concordance with ANA IIF pattern can improve MA test accuracy.

Epstein-Barr virus-related lymphoma in rheumatoid arthritis: implications for long-term usage of immunosuppressive drugs and review of the literature.

BACKGROUND: Rheumatoid arthritis (RA) is a common autoimmune disease where methotrexate (MTX) is widely used as the first-line therapy. The combination of RA and MTX is associated with lymphoproliferative disorders (LPD). RA patients with Epstein-Barr virus (EBV) have impaired T-lymphocyte function, thus allowing an overgrowth of EBV-positive lymphoblastoid cells. We examined the association of EBV with LPD in immunosuppressed RA patients, particularly those treated with MTX. AIM: To review the relationship between RA, EBV-associated LPD and MTX use. METHODS: We reported two cases of RA patients with long-term MTX treatment who subsequently developed EBV-positive LPD, followed by a review of the relevant literature. RESULTS: Compared with normal population, RA patients have a higher risk of lymphoma, with diffuse large B-cell lymphoma being the most common subtype. MTX withdrawal can lead to lymphoma regression. Other biological therapies, such as abatacept and tocilizumab, are not associated with increased EBV-positive lymphoma diagnosis in RA patients. CONCLUSION: The association between EBV, lymphoma and MTX highlights the need to consider reducing or stopping MTX in patients who have had stable RA for many years.

Successful endovascular thrombectomy 90h after stroke onset.

Endovascular thrombectomy (EVT) has extended the conventionally accepted time window of treatment, from 4.5h (ECASS III trial) for intravenous thrombolysis, to 7.3h for EVT (HERMES collaboration). More recent evidence suggests EVT times could be extended to 24h in carefully selected patients (DAWN trial). Some patients present after these time windows with large areas of ischemia but little established infarction on imaging. They represent a major dilemma with much to gain from EVT but at theoretically higher risk of a poor outcome. We present a case of near-complete left M1 occlusion in which EVT achieved reperfusion 90h 41min after stroke onset with excellent clinical outcome. Current guidelines on treatment windows for EVT according to HERMES collaboration do not reflect individual patient factors. In appropriate patients delayed EVT may give positive clinical outcomes.