The diagnosis and misdiagnosis of Sjögren disease.

Although one of the most common systemic autoimmune disorders, Sjögren disease (SjD) may be overlooked in patients presenting with non-specific symptoms or no complaints of sicca symptoms. SjD is not a condition to be missed as patients could present with serious extra-glandular manifestations, including lymphomas. In this article, we discuss the diagnostic pitfalls of this disorder and encourage physicians to consider carefully the 'non-textbook' presentations.

Clinical associations of serum Golgi apparatus antibodies in an immunology laboratory cohort.

INTRODUCTION: Anti-Golgi antibodies (AGAs) are rare antibodies that are found as distinct, polarised cytoplasmic staining on the HEp-2 substrate. METHODS: We performed a review of patients that demonstrated this autoantibody in a large laboratory cohort in Australia. Over a 24-month period, all patients that had a sample submitted for routine antinuclear antibodies (ANAs) that had AGA staining were retrospectively identified. Medical records were perused to identify clinical associations. RESULTS: There were 23 813 ANAs identified with 34 patients (0.14%) demonstrating AGA staining. AGAs were found in a variety of inflammatory disorders, malignancies and liver diseases. They did not associate with any other significant ANA, and in contrast with previous studies, we did not find any association with systemic autoimmune rheumatic diseases. CONCLUSIONS: Anti-Golgi antibodies are rare, non-specific and possibly a bystander phenomenon. Future studies are required to study the origin and longitudinal clinical associations of these autoantibodies.

IgA anti-dsDNA antibodies: A neglected serological parameter in systemic lupus erythematosus.

Anti-double-stranded DNA (anti-dsDNA) autoantibodies are archetypal biomarkers found in systemic lupus erythematosus (SLE). Although they can exist in any isotype, very little is understood about the IgA isotype for which most of our knowledge is derived from observational studies. This review article summarises our knowledge of this autoantibody isotype to date. Attention will be spent on clinical associations as well as its potential links with lupus nephritis for which there is still some controversy. Further understanding of this serological parameter may facilitate diagnosis, prognosis and treatments of systemic lupus erythematosus patients.

CD20+ T cells: an emerging T cell subset in human pathology.

INTRODUCTION: Although CD20 is classically a B cell marker, in the last three decades, dim expression has been noted on a subset of T cells as well that has been independently verified by a number of groups. Our understanding of these cells and their function is not well established. METHODS: A thorough review of original articles on CD20+ T cells was undertaken of Pubmed by using combination of phrases including "CD20+", "CD20-positive" and "T cells". Articles in English were considered, and there was no time restriction. RESULTS: CD20+ T cells express the standard T cell markers and, in comparison to CD20¯ T cells, appear to express greater inflammatory cytokines and markers of effector function. Although the ontogeny of these cells is still being established, the current theory is that CD20 may be acquired by trogocytosis from B cells. CD20+ T cells may be found in healthy controls and in a wide range of pathologies including autoimmune diseases, haematological and non-haematological malignancies and human immunodeficiency virus (HIV) infections. One of the best studied diseases where these cells are found is multiple sclerosis (MS) where a number of therapeutic interventions, including anti-CD20 depletion, have been shown to effectively deplete these cells. CONCLUSION: This review summarises the latest understanding of CD20+ T cells, their presence in various diseases, their putative function and how they may be an ongoing target of CD20-depleting agents. Unfortunately, our understanding of these cells is still at its infancy and ongoing study in a wider range of pathologies is required.

Anti-Ro60 and anti-Ro52/TRIM21: Two distinct autoantibodies in systemic autoimmune diseases.

As iconic and important diagnostic autoantibodies, anti-Ro60 and anti-Ro52/tri-partite motif-containing 21 (TRIM21) make a common appearance in a number of systemic autoimmune disorders such as systemic lupus erythematosus (SLE). These autoantibodies often co-exist together; yet despite their close relationship, there is no evidence that they are physically linked and probably reflect a convergence of separate processes of failed immunological tolerance. Confusingly, they are sometimes classed together as the "SSA" or "Ro" autoantibody system without clear distinction between the two. In this Short Communication, we discuss the diagnostic merits for separate detection and reporting of these two autoantibodies, and discuss avenues for future research. Indeed, further insight into their fascinating origins and pathogenic roles in autoimmunity will surely shed light on how we can prevent and treat devastating autoimmune disorders.

Elevated Serum Tryptase in Non-Anaphylaxis Cases: A Concise Review.

One of the most important blood tests in the field of allergy, mast cell tryptase has numerous diagnostic uses, particularly for anaphylactic reactions and for the diagnosis of mastocytosis. However, there are numerous other non-anaphylactic conditions where clinicians may see elevated serum tryptase (hypertryptasemia) and the practicing clinician ought to be aware of these important differential diagnoses. Such conditions include systemic mastocytosis, hematological malignancies, and chronic kidney disease. This article provides a comprehensive, updated summary on the variety of non-anaphylactic conditions where hypertryptasemia may be seen.

CCR6/CCL20 chemokine axis in human immunodeficiency virus immunity and pathogenesis.

Recent studies in human immunodeficiency virus (HIV) have garnered interest for the role of CC chemokine receptor 6 (CCR6) and its known ligands, CC chemokine ligand 20 (CCL20) and human ß-defensins, in viral entry, dissemination and antiviral immunity. Several studies have suggested that CCR6 may also act as a weak co-receptor of HIV entry, in addition to the canonical CXC chemokine receptor 4 (CXCR4) and CCR5. However, the pathogenic significance has yet to be demonstrated as the observations for preferential infection of CD4+CCR6+ over CD4+CCR6- T cells appear to be independent of CCR6 expression. This indicates means for preferential infection other than CCR6 co-receptor use. Attention has also turned to the inadvertent role of the CCR6/CCL20 axis in attracting key immune cells, including TH17 cells and dendritic cells, to sites of infection and propagating the virus to other sites of the body. This review article will summarize the latest evidence that the CCR6/CCL20 chemokine axis is playing an important role in HIV pathogenesis and immunity. Further work with in vivo studies is needed to establish the biological and, hence, therapeutic significance of these findings.

Direct access colonoscopy: impact of intervention on time to colorectal cancer diagnosis and treatment in North West Tasmania.

BACKGROUND: Direct access colonoscopy (DAC) allows general practitioners to refer directly for colonoscopy, without specialist review. Research suggests DAC reduces times to diagnosis and treatment of colorectal cancer. However, there is no information about outcomes of DAC in Australia. AIM: To determine if DAC in North West Tasmania expedited colorectal diagnosis and treatment. METHODS: Pre-post intervention study evaluating time from referral to diagnosis and definitive treatment. Patient demographic characteristics, referral, colonoscopy and treatment information was retrieved from hospital records. Timelines were investigated in standard referrals (SR), emergency department/inpatient referrals and DAC using survival analysis. RESULTS: Two hundred and six colorectal cancer cases were identified (117 SR, 26 DAC, 48 emergency department/inpatient and 15 unknown pathways). Median time to colonoscopy/diagnosis (DAC 6 weeks vs SR 7 weeks, P = 0.55) or definitive treatment (surgery/chemoradiation) (DAC 8 weeks vs SR 9 weeks, P = 0.81) was not significantly improved with DAC. Among SR only, time to diagnosis was 9 weeks pre-intervention versus 5 weeks post-intervention (P = 0.13), and time to treatment was 11 weeks pre-intervention versus 6 weeks post-intervention (P = 0.07). CONCLUSION: There was no statistically significant improvement in time to colorectal cancer diagnosis or treatment among patients referred through DAC compared to SR. There was a trend towards improved waiting times for SR concurrent with the introduction of the DAC pathway, indicating improvement of all referral processes. DAC may not be effective at expediting colorectal cancer diagnosis if it is not accompanied by strict referral guidelines. Larger evaluations of DAC are required in the Australian context.

A review of the role and clinical utility of anti-Ro52/TRIM21 in systemic autoimmunity.

Anti-Ro52/tripartite motif-containing 21 (TRIM21) is a ubiquitous antibody found in a number of systemic autoimmune conditions including Sjögren's syndrome, systemic lupus erythematosus and systemic sclerosis, appearing in about half of these patients. Once coupled with its closely related antibody, anti-Ro60 as the anti-SSA antibody, anti-Ro52 is emerging as a unique antibody with direct pathogenic disease involvement and distinct clinical properties. As a result, recent attention has turned to this antibody and its clinical associations and utility. There is a suggestion of anti-Ro52 being associated with more clinical and laboratory markers of disease; however, marked disagreements occur about its association with various clinical entities such as interstitial lung disease and Raynaud's phenomena. Nevertheless, with a relative paucity of studies about these across the systemic autoimmunity paradigm, limited confidence can be invested in these conclusions. Although the antibody holds great potential as a biomarker, further studies examining its clinical utility are needed. This paper will review the mechanisms of Ro52 as an autoantigen and the clinical associations of anti-Ro52 in human autoimmunity.

The relationship between CCR6 and its binding partners: does the CCR6-CCL20 axis have to be extended?

Chemokines and their receptors are vital for the trafficking of immune cells. In an orchestrated fashion, up- and down-regulation of chemokines and their receptors contribute to both immune system homeostasis as well as inflammation. The CC chemokine, CCL20 and its cognate receptor, CCR6, are described as one of the few chemokine-receptor pairs that show exclusivity. In our review, we analyze observations which indicate that CCR6 does not have CCL20 as an exclusive ligand as once appreciated. For example, attempts to study the pair, utilizing mainly CCR6-deficient mice, are confounded by a family of non-chemokine ligands known as ß-defensins that can bind to CCR6 and potentially can activate the cell. Therefore, a review of the activities of other potential binding partners of CCR6 is essential for interpretation of the current literature on this matter and for an understanding of their involvement in basic immunology and pathology.

CCR6 and CCL20: emerging players in the pathogenesis of rheumatoid arthritis.

The therapeutic targeting of pro-inflammatory TNF with neutralising biological anti-TNF agents, often in combination with other disease-modifying anti-rheumatic drugs, such as the purine synthesis inhibitor methotrexate has been the first major break-through in the treatment of chronic inflammatory diseases in decades. There are however, side effects and disadvantages of these treatments, such as general immunosuppression as well as therapy resistance in a large proportion of patients. This evokes the wish for other, more specialised forms of treatments. The targeting of chemokines and their receptors to disrupt cell movement specifically has been seen as a promising avenue of therapy for a considerable time. We will discuss one particular chemokine and its receptor, the C-C chemokine ligand CCL20 and the C-C chemokine receptor CCR6, and summarise its genetic and biological role in rheumatoid arthritis (RA). CCR6 has been associated with RA in genome-wide association studies and has been shown to be an interesting candidate for a therapeutic approach, considering its and CCL20's expression patterns within the tissue as well as the immune system.

Suicide and gender ratios in Tasmania (Australia) using the Operationalized Predicaments of Suicide tool, and negative experiences.

OBJECTIVE: To examine coroner's reports of completed suicide in Tasmania with the intention of characterizing the influence of gender and other factors. METHOD: One hundred coroner's reports from Tasmania 2010-2012 were examined and basic demographic details (age, gender), suicide method, medical, psychiatric, psychosocial and drug factors were collected. Data were organized using the Operationalized Predicament of Suicide tool and known risk factors, and analysed using SPSS software. RESULTS: We found an overall male:female ratio of 3:1. When acute mental disorder was identified, the male:female ratio was 1:1. When a history of mental disorder is considered, the ratio becomes 1.44:1. When social/environmental factors triggered the event this changed greatly to 5.57:1. CONCLUSION: Males suicide more frequently than females; but this difference disappears when only those with mental disorder at the time of death are considered, and almost disappears when a history of mental disorder are considered. Higher suicide rates of males are driven by social/environmental stressors. These results have implications for understanding the key drivers of suicide, and developing appropriate preventative strategies.

The Sjögren's Working Group: The 2023 OMERACT meeting and provisional domain generation.

Sjögren's disease (SjD) is a systemic autoimmune exocrinopathy with key features of dryness, pain, and fatigue. SjD can affect any organ system with a variety of presentations across individuals. This heterogeneity is one of the major barriers for developing effective disease modifying treatments. Defining core disease domains comprising both specific clinical features and incorporating the patient experience is a critical first step to define this complex disease. The OMERACT SjD Working Group held its first international collaborative hybrid meeting in 2023, applying the OMERACT 2.2 filter toward identification of core domains. We accomplished our first goal, a scoping literature review that was presented at the Special Interest Group held in May 2023. Building on the domains identified in the scoping review, we uniquely deployed multidisciplinary experts as part of our collaborative team to generate a provisional domain list that captures SjD heterogeneity.