External Quality Assessment (EQA) programs play a crucial role in monitoring laboratory performance, identifying inconsistencies, and promoting the adoption of best practices in autoimmune diagnostics. Over the past decade, this field has undergone substantial evolution, driven by technological advances, enhanced standardisation, and increasing efforts toward harmonisation. This review examines findings from two recent studies assessing the decade-long evolution of autoimmune testing through data from the UK National External Quality Assessment Service (UK NEQAS) programmes. The results highlight considerable progress in the adoption of novel immunoassay technologies and improvements in test standardisation. However, challenges persist, particularly in achieving full harmonisation across laboratories and methodologies.

Although autoimmune conditions are normally recognised by their physical symptoms, on further investigation signs of neuropsychiatric disease may become apparent. While it is possible that the one actually causes the other, it is noteworthy that a similar correspondence can also be traced to the so-called gut-brain axis, perhaps indicating a deeper relationship between the three nominally independent variables of immune system, brain, and gut. Increasingly, as this “triple plague” of related conditions (autoimmunity, poor mental health, and weight gain) has begun to resemble an avalanche, intense speculation has focused on the so-called microbiome: that collection of unicellular pro- and eukaryotes, viruses and mobile genetic elements present, to a greater or lesser extent, at many sites around and inside the body. Primarily for reasons of accessibility and ease of analysis, most effort has focused on the bacteria, i.e., the bacteriome, but unfortunately with little rationale. By contrast, our work was based on the premiss that the microbiome, “our microbes” has evolved to be an intergenerational part of animal immune systems, helping to protect successive generations of multicellular entities against external microbes. Analysis further suggested that key microbes should be the more flexible microeukaryotes, while the concomitant, diverse, bacteriome is able to express mobile genetic elements. In summary, the evolved nature of these key microbes means that they should be transferred at birth, i.e., as a maternal microbial inheritance working alongside the parental genetic inheritance of the individual. As antigenic information is carried within the body by sentinel cells, the most succinct suggestion would be that intergenerational information is carried by means of a microbial version of such cells, perhaps taken up by the neonate gut as a form of inoculation to become what could be classed as an “immune-gut-brain triangle”. If so, it would be their failure in microbe-hostile environments that accounts for the often early-onset epidemiology of what has been termed “dysbiosis”: potentially eczema in the infant; autism in toddlers; and type 2 diabetes in primary school children. Significantly, however, in this hypothesis disease is not a problem of the organs themselves, but of their communication with the brain. Accordingly, the so-called placebo effect could be due to a temporary improvement in brain-centred communication.

Digital clubbing, or hypertrophic osteoarthropathy in its more advanced form, is a distinctive clinical sign characterized by bulbous enlargement of the distal phalanges and increased nail curvature. It is classically associated with neoplastic, infectious, and hepatopulmonary diseases, where tissue hypoxia and circulating angiogenic mediators play central roles. In contrast, rheumatic diseases such as rheumatoid arthritis, systemic sclerosis, and idiopathic inflammatory myopathies, even when complicated by significant pulmonary fibrosis and hypoxemia, rarely present with digital clubbing. This review explores the pathophysiologic mechanisms of clubbing, contrasts them with the pathogenesis of rheumatic interstitial lung disease (ILD), and discusses why autoimmune fibrotic processes may inherently prevent the development of this ancient clinical sign. The rarity of clubbing in autoimmune ILD has diagnostic and pathogenetic implications that extend beyond clinical observation, suggesting fundamental differences in vascular and cytokine regulation compared with neoplastic or infectious fibrosis.

Background. Rheumatoid arthritis (RA) is a chronic autoimmune disease driven by inflammatory pathways involving cytokines and complement activation. Interleukin-6 (IL-6) promotes hepatic synthesis of acute-phase proteins, including complement components C3 and C4. Tocilizumab (TCZ), a humanized monoclonal antibody targeting the IL-6 receptor, has proven effective in RA management. However, its impact on the complement system remains poorly characterized. Methods and Results. We studied 10 patients with moderate-to-severe RA treated with intravenous TCZ (8 mg/kg/month) over 48 weeks. Serum levels of C3, C4, CH50, ESR, and CRP were assessed at baseline and at 4, 12, 24, 36, and 48 weeks. Complement activation was monitored via C3 and factor B split products. A rapid and sustained reduction in C3 and C4 levels was observed starting at week 4, without changes in CH50 or detectable cleavage products. This reduction coincided with significant improvement in inflammatory markers and clinical outcomes (DAS28 and HAQ scores). Conclusions. IL-6R blockade with TCZ is associated with a rapid and sustained reduction in complement proteins C3 and C4. In a proportion of patients, complement levels reached values below the lower limit of normal during follow-up, while CH50 remained stable and complement split products were not detected. These findings are consistent with altered acute-phase/hepatic regulation of complement under IL-6 inhibition rather than overt complement consumption. The clinical significance of complement reduction and its role as a biomarker of treatment response require confirmation in larger studies. 

Environmental triggers, particularly viral infections such as Epstein-Barr virus (EBV), may significantly contribute to the induction or exacerbation of psoriasis (Ps). EBV persists lifelong and is linked to several autoimmune diseases. Nuclear antigen 1 (EBNA-1) helps maintain latency and is a key immune target. Objective: This study aimed to investigate the potential association between EBV infection, specifically the humoral immune response to EBNA-1, and psoriasis by comparing seroprevalence and antibody levels in psoriatic patients versus healthy controls. Methods: A case-control study was conducted involving 23 patients with psoriasis (Ps) and 22 healthy controls (HC). Serum samples were analyzed for the presence of anti-EBNA-1 IgG antibodies using a standard enzyme-linked immunosorbent assay (ELISA). Seropositivity rates were compared using Fisher’s Exact Test, and quantitative antibody levels, expressed as mean ± standard deviation, were compared using an appropriate parametric test. Results: A significantly higher proportion of psoriatic patients were seropositive for anti-EBNA-1 antibodies than healthy controls (95.7% vs. 59.1%, p = 0.004). However, among seropositive individuals, the mean quantitative antibody levels did not differ significantly between the two groups (Ps: 63 ± 25.7 vs. HC: 75.6 ± 31.6, p = ns). Conclusion: Anti-EBNA-1 EBV antibodies are more prevalent in psoriasis compared to healthy controls, and further research is warranted to elucidate the mechanistic role of that viral antigen as a potential contributor to disease-related immune inflammation.