Diagnosis Of Systemic Autoimmune Diseases Research Articles

Metabolomics in the Diagnosis of Systemic Autoimmune Diseases: A MiniReview with a Focus on Psoriatic Arthritis and Rheumatoid Arthritis

Complex and overlapping clinical presentation of systemic autoimmune diseases, such as Psoriatic arthritis (PsA) and Rheumatoid arthritis (RA), creates significant difficulties in early diagnosis and management. Metabolomics, as a rapidly developing field, holds a great potential to identify the intricate metabolic disturbances related to these conditions. This may assist in the early and accurate diagnosis, and personally-tailored treatment of these conditions.

Metabolomics in the Diagnosis of Systemic Autoimmune Diseases: A MiniReview with a Focus on Psoriatic Arthritis and Rheumatoid Arthritis

Complex and overlapping clinical presentation of systemic autoimmune diseases, such as Psoriatic arthritis (PsA) and Rheumatoid arthritis (RA), creates significant difficulties in early diagnosis and management. Metabolomics, as a rapidly developing field, holds a great potential to identify the intricate metabolic disturbances related to these conditions. This may assist in the early and accurate diagnosis, and personally-tailored treatment of these conditions.

Risk of systemic autoimmune diseases with antiarrhythmic drugs in arrhythmia patients: A retrospective cohort study.

The risk factors for systemic autoimmune disease (SAD)s with antiarrhythmic drug(AAD)s in arrhythmia patients are still unclear. This study was discussed this risk factors for SADs with AADs in arrhythmia patients. This study was a retrospective cohort design and analyzed this relationship in an Asian population. Patients without a prior diagnosis of SADs were identified from Taiwan's National Health Insurance Research Database from January 1, 2000 to December 31, 2013. Cox regression models were estimated the hazard ratio (HR) with 95% confidence interval [CI] of SAD. We estimated the data of participants aged ≧ 20 or ≦ 100 years old and free of SADs at baseline. AAD users (n = 138376) had a significantly increased risk of SADs over non-AAD users. There was a significant higher risk of developing SADs in all age and sex categories. The patients who received AADs, the autoimmune disease with the significantly higher risk was systemic lupus erythematous (SLE) (adjusted HR [aHR] 1.53, 95%CI, 1.04-2.26), Sjögren syndrome (SjS) (adjusted HR [aHR] 2.06, 95%CI, 1.59-2.66) and rheumatoid arthritis (RA) (aHR, 1.57, 95%CI, 1.26-1.94). We concluded that there were statistical associations between AADs and SADs, and the higher incidence was SLE, SjS and RA in arrhythmia patients.

Differences in the Clinical Significance of Antinuclear Antibodies According to Titers and Patterns in Children.

This study aimed to evaluate the differences in the clinical significance of antinuclear antibody (ANA) according to their titers and patterns in the diagnosis of systemic autoimmune diseases (AiD) in pediatric patients. Of the 2442 children who had undergone an ANA test, 473 (19.4%) were positive for ANA, of whom 33 (7.0%) were diagnosed with significant AiD. The positive predictive value (PPV) for significant AiD was considerably high on application of an ANA titer of ≥1:640, and the PPV of a dense fine speckled (DFS) pattern was significantly lower compared with those of speckled and homogenous patterns. The diagnostic value of ANA positivity for AiD is limited, and the clinical significance of the DFS pattern is relatively lower compared with that of other patterns, such as homogenous and speckled patterns, in children. It is necessary to approach the significance of ANA in children individually depending on titers and patterns.

ANA-specific antibodies, ANA patterns, anti-ds-DNA results, and clinical diagnosis: a laboratory and clinical audit.

The diagnosis of systemic autoimmune diseases (SAID) is challenging, due to overlapping features with other non-immune disorders. Anti-nuclear antibodies (ANA)/anti-cellular antibodies are the sensitive screening tests but anti-double-stranded-deoxyribonucleic acid-antibody (anti-ds-DNA) and ANA-specific antibodies are specific for SAID. We aimed to look at ANA-specific antibodies in our patients and correlated them with ANA patterns, anti-ds-DNA, and clinical diagnosis for proper interpretation and better patient management cost-effectively. A retrospective data analysis of 641 patients was done (1st of February 2019 to 31st of July 2021) who were tested for ANA-specific antibodies at the Immunology Department of Indus Hospital and Health Network. ANA and anti-ds-DNA results and clinical diagnosis were also analyzed for ANA-specific antibody-positive patients. Descriptive data were presented in mean ± standard deviation and frequency percentages whereas inferential data were analyzed with a chi-square test for association between ANA-specific antibodies status, ANA, anti-ds-DNA, and clinical features. ANA-specific antibodies test revealed positivity for at least one autoantibody in 245 (38.2%) patients. Of these, ANA was tested in 206 patients reactive for ANA-specific antibodies and found positive in 195 (95%) as compared to negative (< 0.001). Speckled and homogenous were predominant ANA patterns in ANA-specific antibody-positives (56% and 42% respectively). Multiple ANA patterns were found in 18 patients most commonly with systemic lupus erythematosus (SLE) and mixed connective tissue disorder (MCTD). Anti-SSA were the most common ANA-specific antibodies (50%) and were mostly found in sera with speckled (61/97) and homogenous (38/97) patterns and associated mostly with SLE (48%) and Sjogren's syndrome (86%). Among ANA-negative patients, anti-SSA were the most common antibodies (n = 5). Anti-ds-DNA was found in 66% of SLE patients along with another ANA-specific antibody. This study showed that testing for ANA-specific antibodies cannot be gated on ANA patterns. Also, there is a redundancy of these antibodies with various clinical diagnoses. Moreover, they are useful in making a diagnosis in ANA-negative patients as well with clinical suspicion.

Procalcitonin for the early discrimination of fever etiology in patients with systemic autoimmune diseases attending the emergency department.

In febrile patients with known systemic autoimmune disease, early discrimination between infection and disease flare often represents a clinical challenge. This study aimed at evaluating the efficacy of procalcitonin (PCT) and other common inflammatory biomarkers in discriminating disease flare from bacterial infections in the Emergency Department (ED). In a cross-sectional observational retrospective study, we identified consecutive febrile patients with a known diagnosis of systemic autoimmune disease, admitted to the ED, and subsequently hospitalized. Flare vs infective disease was defined on clinical records at hospital discharge. Dosage of common inflammatory markers was performed at ED admission. Out of 177 patients, those with infection were most commonly elderly, frail, and with reduced peripheral oxygen saturation at admission. When compared to C-reactive protein (CRP) and white blood count (WBC), PCT showed the best performance in discriminating infections vs flare. However, only at a very high threshold value of 2ng/ml, the PCT had a satisfactory negative predictive value of 88.9%, although with a very low specificity of 13.6% and a positive predictive value of 35.8%. Our data suggest that in the ED setting, the early PCT determination has low accuracy in the differentiation of disease flare from infection in patients with known rheumatologic disease. However, the PCT could be useful in elderly and comorbid subjects, in supporting clinical assessment and in recognizing those febrile patients needing prompt antibiotic treatment.

The Anti-Cytoplasmic and Anti-Mitotic Autoantibodies; Are These Antibodies Associated with Diseases?

Examination of antinuclear antibody (ANA) is used in diagnosis of systemic autoimmune diseases, and the indirect immunofluorescence (IIF) assay using HEp-2 cells is the gold standard method. HEp-2 allows the detection of multiple target antigen-directed autoantibodies. The guide “The International Consensus on ANA Patterns (ICAP)”, characterizes the patterns into three groups: nuclear, cytoplasmic, and mitotic. The majority of these are associated with autoimmune diseases, but some are rarely seen in autoimmune diseases or may be associated with conditions other than autoimmune disease. There is no consensus on how to report cytoplasmic and mitotic patterns-negative or positive. We aimed to examine the characteristics of patients that had cytoplasmic or mitotic staining in ANA evaluation by IIF. In our Medical Microbiology Laboratory, 18985 ANA tests of 16940 patients were studied between 01.01.2015-31.12.2019. Cytoplasmic or mitotic pattern was detected in 393 (2.07%) tests belonging to 385 patients. Cytoplasmic patterns suggestive of anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (ASMA), anti-Jo-1 and anti-ribosomal P-protein were not included. The most common patterns were anti-midbody, anti-spindle fibers, and anti-vimentin patterns. There were 66 rheumatology patients that were negative for ANA but had cytoplasmic or mitotic staining. There was no statistically significant difference between the diagnosis and patterns of these patients. We suggest that the ANA should be reported as “negative” in case of cytoplasmic or mitotic pattern unless the term anti-cell antibody is used. It should be noted in the description part of the report in order to distinguish significant cytoplasmic patterns and give an idea for some specific conditions.

The Relationship between 9/11 Exposure, Systemic Autoimmune Disease, and Post-Traumatic Stress Disorder: A Mediational Analysis.

The relationship between 9/11 exposure, systemic autoimmune disease (SAD) and mental health remains poorly understood. This report builds on a prior analysis of World Trade Center Health Registry data to determine whether 9/11 exposure is associated with higher risk of SAD, and if so, whether post-traumatic stress disorder (PTSD) is a mediating factor and whether the association varies by responder/community member status. The final analytic sample comprised 41,656 enrollees with 123 cases of SAD diagnosed post 9/11 through November 2017. SAD diagnosis was ascertained from survey responses and confirmed by medical record review or physician survey. Logistic regression models were constructed to determine the relationship between 9/11 exposure and PTSD and SAD. Causal mediation analysis was used to determine the mediational effect of PTSD. Each analysis was stratified by 9/11 responder/community member status. Rheumatoid arthritis (n = 75) was the most frequent SAD, followed by Sjögren’s syndrome (n = 23), systemic lupus erythematosus (n = 20), myositis (n = 9), mixed connective tissue disease (n = 7), and scleroderma (n = 4). In the pooled cohort, those with 9/11-related PTSD had 1.85 times the odds (95% CI: 1.21–2.78) of SAD. Among responders, those with dust cloud exposure had almost twice the odds of SAD, while among community members, those with 9/11-related PTSD had 2.5 times the odds of SAD (95% CI: 1.39, 4.39). PTSD was not a significant mediator. Although emerging evidence suggests 9/11 exposure may be associated with SAD, more research is needed, particularly using pooled data sources from other 9/11-exposed cohorts, to fully characterize this relationship.

AB1152 COVID-19 mRNA VACCINE BOOSTER IN PATIENTS WITH SYSTEMIC AUTOIMMUNE DISEASES

BackgroundPatients with systemic autoimmune diseases (SADs) are often treated with drugs that interfere with the immune system and previous data showed a reduced seroconversion rate after anti-SARS-CoV2 vaccine in these subjects compared to healthy controls1. Administration of a booster dose of the vaccine could be particularly important in these patients, but data available to date are still scarce.ObjectivesTo evaluate the antibody response to the booster dose of mRNA SARS-CoV2 vaccine in patients with SADs and to compare it to the response after completion of the first vaccination course. Secondly, to find possible correlations between a low antibody titre and patients’ clinical features, with special regard to ongoing immunosuppressive therapies.MethodsConsecutive patients with an established diagnosis of SADs undergoing SARS-CoV2 vaccine were prospectively enrolled from January 2021; among them, we selected the patients who received the third vaccination dose between September and December 2021. Demographic and clinical data were collected at enrolment (sex, age, diagnosis, disease duration, ongoing therapies, previous SARS-CoV2 infection, presence of hypogammaglobulinemia); the last three elements were reassessed at each follow-up visit. Blood samples were collected 4 weeks both after the second (W4a) and the third (W4b) dose of the vaccine; a minority of patients was also tested 12 weeks after the second dose (W12). IgG antibodies to SARS-CoV2 receptor-binding domain (RBD) and neutralizing antibodies inhibiting the interaction between RBD and angiotensin converting enzyme 2 were evaluated. IgG anti-RBD were detected by solid phase assay on plates coated with recombinant RBD, while neutralising antibodies by using the kit SPIA (Spike Protein Inhibition Assay). Cut-off values were defined as the 97.5th percentile of a pre-vaccine healthy population. Statistical analysis was performed using IBM SPSS Statistics 20 and GraphPad Prism statistical packages. P values &lt;0.05 were considered significant.ResultsForty-five patients (95.6% female; mean age ±SD 55.6±14.1 years; mean disease duration 12.9±10.6 years) were enrolled. Diagnosis was in most cases connective tissue disease (31/45, 68.9%), followed by inflammatory arthritis (11/45, 24.4%) and systemic vasculitis (3/45, 6.7%). Two patients (4.4%) had a previous SARS-CoV2 infection and three had hypogammaglobulinemia (6.7%). At the time of the second dose, 18/45 patients were treated with glucocorticoids (GCs) [mean daily 6-methylprednisolone (6MP) dose 3.9 mg (min. 2, max. 14)], 17/45 with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and 12/45 with biologic DMARDs (bDMARDs). At the third dose administration, 19/45 patients were treated with GCs [mean daily 6MP dose 4.1 mg (min. 1.5, max. 10)], 18/45 with csDMARDs and 13/45 with bDMARDs. Anti-RBD IgG were positive in 42/45 patients (93.3%) at W4a, in 16/18 (88.9%) at W12 and in 42/45 (93.3%) at W4b. Neutralizing antibodies were present in 38/45 patients (84.4%) at W4a, in 14/18 (77.8%) at W12 and in 42/45 (93.3%) at W4b. Both anti-RBD IgG titers and neutralizing antibody titers significantly increased after the third dose if compared to W4a (p&lt;0.0001 both) (Figure 1). Interestingly, of the 7 patients who had not developed an adequate neutralizing antibody response after the first vaccination course, 5 mounted an adequate titer after the booster. Two non-responder patients were both on combination therapy (one with low dose of GCs plus mycophenolate mofetil, the other with methotrexate and infliximab).ConclusionOur data suggest that in patients with SADs there is a decline in the antibody titers developed after COVID-19 vaccination, however the booster dose is effective in restoring an adequate antibody titre. These data consolidate the importance of a booster dose of COVID-19 vaccination in patients with SADs to aid in the generation of an immune response.

Antinuclear antibodies (ANA) as a criterion for classification and diagnosis of systemic autoimmune diseases

The classification and diagnosis of systemic autoimmune diseases are frequently based on a collection of criteria composed of clinical, laboratory, imaging, and pathology elements that are strongly associated with the respective disease. Autoantibodies are a distinctive hallmark and have a prominent position in the classification criteria of many autoimmune diseases. The indirect immunofluorescence assay on HEp-2 cells (HEp-2 IFA), historically known as the antinuclear antibody test, is a method capable of detecting a wide spectrum of autoantibodies. A positive HEp-2 IFA test is part of the classification criteria for systemic lupus erythematosus (SLE) and juvenile idiopathic arthritis (JIA), as well as the diagnostic criteria for autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC). A positive HEp-2 IFA test can appear as different morphological patterns that are indicative of the most probable autoantibody specificities in the sample. Only some of the HEp-2 IFA patterns are associated with the specific autoantibodies relevant to SLE, JIA, AIH, and PBC, whereas some other patterns occur mainly in non-related conditions and even in apparently healthy individuals. This paper provides a critical review on the subject and proposes that the classification and diagnostic criteria for SLE, JIA, AIH, and PBC could be improved by a modification on the HEp-2 IFA (ANA) criterion in that the staining patterns accepted for each of these diseases should be restricted according to the respective relevant autoantibody specificities.

Association between clinical phenotypes of dermatomyositis and polymyositis with myositis-specific antibodies and overlap systemic autoimmune diseases.

The aim of this study was to evaluate the association between clinical phenotypes of dermatomyositis (DM) and polymyositis (PM) with myositis-specific antibodies (MSAs), and overlap diagnosis of systemic autoimmune diseases.This cross-sectional study was conducted on 67 patients with DM and 27 patients with PM recruited from a regional hospital in southern Taiwan. Clinical phenotypes of DM and PM were assessed and MSAs were measured using a commercial line blot assay. The association of clinical phenotypes of DM and PM with MSAs and overlap diagnosis of systemic autoimmune diseases was performed using univariate and multiple logistic regression analyses.Clinically, patients with DM and PM and overlap diagnosis of systemic sclerosis were associated with a higher risk of interstitial lung diseases (ILDs) (odds ratio [OR] = 6.73; P = .048), Raynaud phenomenon (OR = 7.30; P = .034), and malignancy (OR = 350.77; P = .013). The risk of malignancy was also associated with older age (OR 1.31; P = .012), and male patients were associated with a higher risk of fever. For MSAs, anti-aminoacyl-tRNA synthetase antibodies were associated with ILD, antinuclear antibody were associated with a lower risk of arthritis, anti-transcription intermediary factor 1-gamma antibodies were associated with milder symptoms of muscle weakness, anti-Ku antibodies were associated with overlap diagnosis of systemic lupus erythematosus, and anti-Ro52 antibodies were associated with the development of Raynaud phenomenon and Sjögren syndrome.MSAs and overlap diagnosis of systemic sclerosis were significantly associated with clinical phenotypes of DM and PM. Physicians should be vigilant for malignancy in older DM and PM patients with overlap diagnosis of systeic sclerosis. The possibility of developing ILD in patients with overlap diagnosis of systemic sclerosis or serum positivity of anti-aminoacyl-tRNA synthetase antibodies should be considered.

Incidence and predictors of COVID-19 and flares in patients with rare autoimmune diseases: a systematic survey and serological study at a national reference center in France

BackgroundThe risk of severe COVID-19 and its determinants remain largely unknown in patients with autoimmune and inflammatory rheumatic diseases. The objective of this study was to assess the prevalence of COVID-19 infection in patients followed for rare autoimmune diseases as well as the predictors of COVID-19 and disease flare-ups.MethodsCross-sectional phone survey from April 9, 2020, to July 2, 2020, during which patients with autoimmune diseases followed at the National Reference Center for Rare Autoimmune diseases of Strasbourg were systematically contacted by phone and sent a prescription for a SARS-CoV-2 serology.ResultsOne thousand two hundred thirty-two patients were contacted. One thousand fifty-five patients with a confirmed diagnosis of systemic autoimmune disease were included (4 unreachable, 4 moves abroad, 5 deaths before pandemic, 50 without consent, and 114 without autoimmune disease). Among them, 469 (44.5%) patients were tested for SARS-CoV-2 serology.Thirty-nine patients (7.9%) had SARS-CoV-2 infection (either through chest CT-scan [n = 5], RT-PCR on nasopharyngeal swab [n = 14], or serology [n = 31]) among the 496 who underwent at least one of those 3 diagnosis modalities. Of the 39 proven cases, 33 had clinical manifestations (6 asymptomatic patients were diagnosed through systematic serology testing), 31 were managed by home care, 3 were hospitalized due to a need for oxygenation, two required admission to an intensive care unit, and one died. Among patients with confirmed SARS-CoV-2 infection, reported flares were more frequent than in uninfected patients (26.3% [10/38] vs. 7.0% [32/457], p < 0.0001). Preventive sick leave had no significant impact on the prevalence of SARS-CoV-2 infection (5.8% [3/53]) compared to work continuation (7.6% [30/397], p = 0.64).Overall, the seroprevalence of SARS-CoV-2 was 6.6% (31/469) which was numerically lower to the Grand-Est general population estimated to be 9.0%.ConclusionsThis systematic survey of more than 1000 patients with rare systemic autoimmune diseases reports a low prevalence of proven SARS-CoV-2 infection and very rare severe infections, probably related to good compliance with prophylactic measures in these patients.

Non-organ-specific autoimmunity in adult 47,XXY Klinefelter patients and higher-grade X-chromosome aneuploidies.

Current literature regarding systemic autoimmune diseases in X-chromosome aneuploidies is scarce and limited to case reports. Our aim was to evaluate the frequency of anti-nuclear (ANAs), extractable nuclear (ENA), anti-double-stranded DNA (dsDNAs), anti-smooth muscle (ASMAs) and anti-mitochondrial (AMAs) antibodies in a large cohort of adults with Klinefelter's syndrome (KS, 47,XXY) and rare higher-grade sex chromosome aneuploidies (HGAs) for the first time. Sera from 138 X-chromosome aneuploid patients [124 adult patients with 47,XXY KS and 14 patients with HGA (six children, eight adults)] and 50 age-matched 46,XY controls were recruited from the Sapienza University of Rome (2007-17) and tested for ANAs, ENAs, anti-dsDNAs, ASMAs and AMAs. Non-organ-specific immunoreactivity was found to be significantly higher in patients with 47,XXY KS (14%) than in the controls (2%, p=0.002). Among all the antibodies investigated, only ANAs were observed significantly more frequently in patients with 47,XXY KS (12.1%) than in the controls (2%, p=0.004). No anti-dsDNA immunoreactivity was found. Stratifying by testosterone replacement therapy (TRT), non-organ-specific autoantibody frequencies were higher in TRT-naive (p=0.01) and TRT-treated groups than in controls. No patients with HGA were found positive for the various autoantibodies. Non-organ-specific autoantibodies were significantly present in 47,XXY adult patients. Conversely, HGAs did not appear to be target of non-organ-specific immunoreactivity, suggesting that KS and HGAs should be considered as two distinct conditions. The classification and diagnosis of systemic autoimmune diseases is frequently difficult. To support a correct clinical evaluation of KS disease and to prevent eventual secondary irreversible immune-mediated damages, we highlight the importance of screening for non-organ-specific autoimmunity in Klinefelter's syndrome.

International Consensus on Antinuclear Antibody em Portugal

Introdução: A pesquisa de autoanticorpos em células HEp-2 através de imunofluorescência indireta é o teste padrão atualmente aceite como a ferramenta central para o diagnóstico das doenças autoimunes sistémicas. O International Consensus on Antinuclear Antibody (ANA) Patterns tem como objetivo principal alcançar um consenso na nomenclatura e na descrição dos diferentes padrões morfológicos de anticorpos antinucleares. Este trabalho tem como objetivo ampliar o projeto do International Consensus on ANA Patterns de forma a estabelecer um consenso em Portugal para a sua nomenclatura, procurando contribuir para a harmonização no diagnóstico autoimune e promover a qualidade diagnóstica nas doenças reumáticas sistémicas autoimunes.Material e Métodos: Os laboratórios participantes identificaram cada designação de padrão citoplasmático e nuclear do International Consensus on ANA Patterns (incluindo o código padrão anti-célula), e fizeram corresponder a cada uma a respetiva nomenclatura portuguesa em uso. Os resultados foram agregados e serviram de base ao trabalho de harmonização da nomenclatura. Seguiram-se reuniões de consenso, num processo iterativo até à redação de uma proposta final consensualizada.Resultados: A concordância prévia entre laboratórios era superior a 75% para 23 do total de 29 padrões anti-célula. O grau em que cada laboratório está alinhado com a referência internacional do International Consensus on ANA Patterns varia entre 22,1% e 100%. Foi possível elaborar uma versão consensualizada da nomenclatura do International Consensus on ANA Patterns para Portugal.Discussão: Existia uma boa base de consenso para a nomenclatura do International Consensus on ANA Patterns, mas com diferenças importantes em algumas das traduções da terminologia. O estudo realça a necessidade de colaboração entre laboratórios para uma descrição inequívoca dos resultados laboratoriais.Conclusão: Este trabalho mostra o potencial positivo da colaboração entre laboratórios para gerar consensos que contribuam para a melhoria do diagnóstico e acompanhamento dos doentes.

Antinuclear Antibody Profiling in Patients of a Tertiary Care Centre in Central India.

The incidence of autoimmune disorders that includes the connective tissue diseases has seen a rise in India in recent times. Antinuclear antibodies, the telltale sign of systemic autoimmune response, thus can be used as a screening tool and also to support the diagnosis of systemic autoimmune disease. The present retrospective cross- sectional analysis aimed to study the antinuclear antibodies profile (patterns and specific antibody reactivity) amongst suspected cases of auto-immune disorders at a tertiary care teaching hospital. The study retrieved and reviewed reports of 644 patients sent for ANA testing by indirect immunofluorescence assay over a period of 1year by different specialty departments. Positive samples were further processed for anti-ds-DNA antibody and antibodies to extractable nuclear antigen. Data collected was statistically analysed. ANA pattern positivity was observed in 31% of cases and a positive antibody reactivity was seen in 66% of them. Female predominance (82%) was noted in both pattern positivity and antibody reactivity. High levels of pattern positivity and antibody reactivity was found in the young adults (45.9%). Amongst the ANA patterns, the nuclear homogenous pattern was found the commonest. The common antibodies associated with this pattern were anti-dsDNA and U1 Sm/RNP antibodies. A stronger fluorescence intensity on initial screening showed a higher confirmation rate for specific antibodies on immunoassay. High occurrence of positive ANA patterns in autoimmune disorders suggests its utilization as a screening tool for them and would also play an adjuvant to the diagnosis. Early knowledge about future autoimmunity will earn better prognostic achievements through better treatment interventions.

Noninfectious Autoimmune Scleritis: Recognition, Systemic Associations, and Therapy.

The aim of this review is to provide the information necessary for recognizing scleritis in rheumatology patients, recognize associated systemic diseases in scleritis patients referred to rheumatology, and choose the best conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or biologic therapy, based on the most recent data. Scleritis is most often associated with systemic conditions, particularly autoimmune conditions. Rheumatologists should be most vigilant about rheumatoid arthritis and ANCA-associated vasculitis. A recent systemic association has been found with IgG4-related disease as well. Most of the therapeutic decisions are based on observational data. Most recently, there is increasing evidence of the role of rituximab for refractory disease. Scleritis is a severe inflammatory ocular condition that leads to complications including vision loss. It can precede a systemic autoimmune disease diagnosis, especially in the case of vasculitis. Prompt recognition and adequate therapy are needed in order to avoid serious ocular complications. There is an unmet need for (1) head-to-heat trials on csDMARDs and biologic drugs for the treatment of idiopathic scleritis and (2) randomized controlled trials on the treatment of refractory cases.

Rare immunofluorescence patterns of autoantibodies on HEp-2 cells defined by ICAP identify different autoimmune diseases in the absence of associated specificities: a Spanish multicentre study.

ANA are the most extensively used test for the diagnosis of systemic autoimmune diseases. However, testing by indirect immunofluorescence assays (IIFAs) on HEp-2 cells, the gold standard test, is time-consuming and needs expertise. Thus there is a trend to replace it with other automated solid-phase assays directed against specific ANA. Nonetheless, the Hep-2 cell is an autoantigen array and ANA have been classified into 29 types, some of them with no clear association with a specificity to be detected. It is especially in these uncommon patterns where no clinical relationship is found and no antigenic specificity is detected. Here we retrospectively collected clinical data from patients with confirmed uncommon HEp-2 IIFA patterns to search for an associated clinical condition. We conducted an observational retrospective study including 608 patients with organ-specific and non-organ-specific autoimmune diseases (OSADs and NOSADs, respectively) with a confirmed rare pattern of ANA detected by IIFA on HEp-2 cells in the routine practice of the Spanish European Autoantibodies Standardization Initiative laboratories. Inclusion criteria are the existence of a minimum follow-up of 2 years and the availability of clinical data. Nuclear patterns were more frequent in SLE (P = 0.001) and SS (P = 0.001), whereas the cytoplasmic ones were significantly higher in SSc (P = 0.022) and inflammatory myositis (P = 0.016). Mitotic patterns did not show any preferences for a specific disease and 62.7% of them corresponded to the nuclear mitotic apparatus pattern (AC-26). The most frequent NOSADs in patients with the AC-26 pattern were SLE (28.6%), SS (11.9%) and RA (11.9%). The cytoplasmic HEp-2 IIFA patterns were equally distributed in both groups of patients. In the OSAD patients there was no predominant pattern, except for AC-6 in primary biliary cholangitis due to Sp-100 antibodies (P < 0.001). Detection of infrequent ANA might be a unique finding with no disease-associated specificities and could lead to the suspicion of an autoimmune disease.

Pleuropulmonary manifestations of systemic autoimmune diseases: An 84-case series analysis

Introduction. The systemic autoimmune diseases (SAD) can cause a variety of pulmonary and pleural abnormalities. The aim of this paper is to review clinical and radiological characteristics of a series of patients with a systemic autoimmune disease hospitalized at a tertiary level facility. Methods. In this retrospective study, we reviewed the clinical and imaging findings in patients diagnosed with SAD at the Teaching Hospital of Pulmonology during a nine-year period. Results. An 84-patient group (mean age of 53.8 years) consisted of 64 women and 20 men. Fifty-eight out of 84 patients suffered from collagen vascular disease (CVD) and 26/84 had systemic vasculitis. Fatigue was the dominant symptom (75.8% in CVD, and 69.2% in vasculitis). Cough, hemoptysis, and fever were more frequent in patients with vasculitis. Fibrosis was the most common radiological manifestation of CVD (26/58), followed by pleural effusion (18/58) and consolidation (10/58). Irregular opacities were dominant radiologic finding in vasculitis (10/26), followed by nodules (8/26). Histological confirmation of systemic autoimmune disease was obtained in 28.6% patients, in 58/84 patients the diagnosis was based on a positive serologic test and clinico-radiological manifestations, in two cases on clinical and radiological features according to defined criteria. Conclusion. Pleuropulmonary manifestations of SAD are usually expressed in the sixth decade of life, predominantly in women. Clinical findings and positive serologic tests suggest diagnosis of SAD. Fibrosis is the most common radiologic pattern found in almost one half of the patients with CVD and irregular opacities are the most common findings in vasculitis.

Comparison of two automated antinuclear antibodies screening for the diagnosis of systemic autoimmune diseases

Immunisation is one of the most successful interventions for controlling infectious diseases but relies on continuous high coverage. Parental vaccine refusal and logistical barriers to access are threats to the success of immunisation programs, with resultant population immunity gaps leading to outbreaks of vaccine-preventable diseases. In Indonesia, coverage of childhood vaccines is suboptimal, with poor coverage of diphtheria-tetanus-pertussis vaccine leading to a large diphtheria outbreak in 2017.To explore the underlying parents’ reasons for incomplete childhood immunisation in Indonesia, semi-structured interviews were conducted in Tangerang Selatan, Banten Province, Indonesia. Sixteen purposively selected primary carers of partially and unimmunised children were interviewed. Transcripts were coded and analysed using inductive thematic analysis.Parental reasons were categorised into three interrelated themes of belief barriers, safety concerns, and issues of trust and misinformation. Stark differences were evident in reasons provided by carers of unimmunised children compared to partially immunised children. For parents of unimmunised children, Islamic beliefs, belief in the strength of natural immunity, and the use of alternative medicines strongly influenced behaviours. Safety concerns, issues of trust including distrust in the government, misinformation, and trust in information obtained through social networks were also prominent. In contrast, concerns about mild side-effects and logistical barriers outweighed beliefs among carers of partially immunised children.Our findings highlight the complexities in decision making for parents who decide not to vaccinate their children. In the Indonesian context, public health education and engagement of religious leaders to bridge the gap between religious beliefs and vaccine acceptance are needed to address vaccine refusal. Future research on the influence of social networks on vaccine hesitancy in the Indonesian context is also warranted. For parents of partially vaccinated children, interventions should focus on barriers of access to community health staff to encourage timely schedule completion.

Statistički pristup izboru optimalnih parametara u dijagnostici nekih bolesti vezivnog tkiva

In order to choose the optimal parameters for easier diagnosis of systemic autoimmune diseases, the authors focused on data dimensionality reduction, using both feature selection and feature extraction. The Multiple Correspondence Analysis was used as a feature extraction method, with the aim of exploring the underlying data structure and detecting the crucial latent variables. The obtained latent variables were used as an input for the Discriminant Analysis which correctly classified 86.5% of all analyzed cases. The high rate of correctly classified objects indicates that it would be possible to automate diagnostic processes, which would lead towards the development of decision support systems in this area of medicine. In addition to their knowledge and experience, clinical experts would have further help in decision support systems. That can allow easier learning, faster checking of diagnostic steps, lower rates of misdiagnosed cases and easier communication with experts from other medical centers.