For antinuclear antibody (ANA) screening, the gold standard method is an indirect immunofluorescence assay (IIFA) using HEp-2 cells, and a serial dilution test is needed to determine the endpoint titer. We aimed to evaluate the accuracy of the estimated endpoint titer (eEPT) by the NOVA View system, by comparing it with the EPT by the serial dilution method (dEPT). The endpoint titers of a total of 1518 ANA positive cases with five major patterns including speckled, homogeneous, centromere, nucleolar, and nuclear dots patterns were determined using both the estimation function and the serial dilution method by the NOVA View system. A significant correlation between the light intensity unit (LIU) values and dEPTs was identified in all five patterns with high ρ values, ranging from 0.666 to 0.832. However, the overall exact match rate between dEPT and eEPT was 22.1% (336/1518), with the ±one-titer match rate being highest in the centromere pattern (62.8%, 81/129), and lowest in the homogeneous pattern (37.6%, 200/532). This suggests that while LIU values correlate well with dEPT, there are discrepancies in numerical agreement. Most cases that did not show an exact match, showed one-to-three-titer overestimations by eEPT. Therefore, adjusting eEPT downward significantly improved the concordance rates with dEPTs. Further investigation for an appropriate cutoff of LIU values for determining eEPT should be performed for clinical application and contribution to the standardization of the ANA titer.

BACKGROUND: Premature ovarian insufficiency (POI) is extremely rare in the early stage of undifferentiated connective tissue disease. Patients with POI find it difficult to achieve successful pregnancy and delivery.
METHODS: A 27-year-old female visited an outpatient department for premature ovarian insufficiency (POI) and infertility. She had regular menstrual periods since she was 14 years old and had no history of systemic disease. Laboratory tests showed low estrogen (15 ng/L, range 19.6-144.2 ng/L), elevated follicle-stimulating hormone (34 U/L), low anti-Mullerian hormone (0.1 μg/L), normal prolactin (11.48 ng/mL), and thyroid stimulating hormone (TSH) levels (0.97 mU/L). She demonstrated smaller bilateral ovarian volume and positivity to antinuclear and antiphospholipid antibodies. After the failure of conventional drug therapy and in vitro fertilization, the patient became pregnant naturally after treatment with glucocorticoids.
CONCLUSIONS: Immunosuppression could help improve ovarian function and pregnancy outcomes in POI patients, but the therapeutic mechanisms are not clear and should be elucidated with more clinical studies.

We evaluated the prevalence of systemic sclerosis (SSc)-related autoantibodies and their clinical significance and compared the sensitivity of two line immunoblot assays on a prospective study group of 96 Polish SSc patients (ACR-EULAR 2013 criteria) whose sera were assessed by indirect immunofluorescence (HEp-2 and monkey liver) and line immunoblot assays: ANA Profile 3 and Systemic Sclerosis Profile by EUROIMMUN (Lübeck, Germany). Organ involvement was evaluated according to the EUSTAR Minimal Essential Data Set. The following autoantibodies’ prevalence was found: Scl-70 (36%), Ro-52 (28%), CENP-B (22%), CENP-A (20%), PM-Scl-75 (20%), PM-Scl-100 (14%), fibrillarin (7%), Th/To (7%), RNA polymerase III 11 kDa (5%), RNA polymerase III 155 kDa (3%), PDGFR (3%), NOR-90 (2%), and Ku (1%). Significant associations between the autoantibodies’ presence and organ involvement were found: ATA (dcSSc > lcSSc, less prevalent muscle weakness), Ro-52 (gangrene, DLCO < 60), CENP-B and A (lcSSc > dcSSc, normal CK), CENP-B (rarer digital ulcers and joint contractures), PM-Scl-100 and 75 (PM/SSc overlap, CK increase, muscle weakness, muscle atrophy), PM-Scl-100 (dcSSc unlikely), PM-Scl-75 (lung fibrosis), fibrillarin (muscle atrophy, proteinuria, conduction blocks, palpitations), Th/To (proteinuria, arthritis, muscle weakness, and rarer esophageal symptoms), RNA Polymerase III 11 kDa (arterial hypertension, renal crisis), RNA polymerase III 155 kDa (renal crisis), and PDGFR (dcSSc, tendon friction rubs). Additionally, the Systemic Sclerosis Profile was significantly more sensitive in detecting SSc-related autoantibodies than ANA Profile 3 (p = 0.002). In conclusion, individual autoantibodies associated with specific characteristics of SSc.

Systemic lupus erythematosus (SLE) is a connective tissue disease of unknown etiology that predominantly affects women of childbearing age. We report a case of male systemic lupus erythematous with antinuclear antibodies and typical clinical presentations of multiple skin lesions, polyarticular joint pain, fatigue, anorexia, and hair loss. Full evaluations were used to establish a diagnosis of SLE. The lower prevalence of SLE among males and antinuclear antibody-negative patients poses a great challenge for diagnosis. Therefore, as primary care doctors, we need to have a high suspicion of systemic lupus erythematous even in male and antinuclear antibody-negative patients. Thus, early treatment may help patients improve their quality of life.

Severe coronavirus disease 2019 (COVID-19) is known to be associated with thrombotic events like ischemic stroke. However, in the case of mild or asymptomatic disease, a thrombotic event like ischemic stroke is rare and has never been reported in our country. We present the case of a 28-year-old male patient with no co-morbidities who was diagnosed to have ischemic stroke involving the basilar artery. No risk factors for ischemic stroke could be found except for post-COVID-19 status, evident by the presence of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

BACKGROUND: Anti-nuclear antibody (ANA) testing is most commonly ordered by general pediatricians to evaluate children with musculoskeletal system complaints. Given the limited utility of the test, we aimed to estimate the effectiveness of ordering ANA testing in childhood.
METHODS: Children referred to our department to be examined due to positive ANA findings between 2008 and 2020 were included in the study. Those with less than one-year follow-up period, those with previously known rheumatic or autoimmune disease, and those diagnosed as an autoimmune and/or rheumatic disease at the first visit were excluded. Data were obtained from their medical records, retrospectively. The parents of all of the patients were called via phone, data were verified, and missing information was collected.
RESULTS: Three hundred and fifty-eight patients (230 females) were eligible for the study. The median age of positive ANA findings was 9.31 (1.3-17.86) years and the median follow-up duration was 4.85 (1-11.91) years. Most of the patients had no underlying disease (n = 337, 94.1%). The most common reason for ordering ANA testing was to evaluate musculoskeletal system symptoms (n = 225, 62.8%). None of our patients referred to us due to positive ANA findings developed any autoimmune conditions or ANA associated rheumatic disease. Hypermobility syndrome is the most common final diagnosis among our ANA-positive patients.
CONCLUSIONS: We suggest that instead of using it as a screening tool, ANA testing should be performed only if there is a strong suspicion of autoimmune diseases or certain rheumatic conditions, such as systemic lupus erythematosus.

UNASSIGNED: To evaluate the prevalence of a spectrum of autoantibodies in adult patients with non-infectious uveitis compared to healthy controls.
UNASSIGNED: This is a case-control study conducted in a tertiary referral center. Serum positivity to auto-antibodies directed at membranous phospholipids (aPL), nuclear antigens, and cytoplasmic (ANCA) antigens were assessed in sera from 63 non-infectious uveitis patients, and 78 healthy controls. Uveitis patients\' demographic and clinical data were collected retrospectively from their medical charts.
UNASSIGNED: Of the spectrum of antibodies evaluated only aPL were linked with uveitis (OR 11.2, CI 1.4-92.1), as 13 (20.6%) uveitis patients were positive to at least one of the screened aPL, namely either anti-cardiolipin (aCL), anti-β2-glycoprotein (aβ2GPI), or anti-phosphatidylserine/prothrombin (aPS/PT). aCL antibodies were detected in 5/63 (7.9%) of uveitis patients and in none of controls (p = 0.016). Positivity to either aCL or aβ2GPI was noted in 8/63 (12.7%) of uveitis patients and in 1 (1.3%) of the controls (p = 0.011). Of the 13 uveitis patients positive to any of the aPL antibodies, 8 (62%) had exclusively anterior uveitis, 9 (69%) were idiopathic, and none had evidence of posterior vaso-occlusive involvement or systemic thrombotic manifestations.
UNASSIGNED: An association between aPL and uveitis among an unselected population of patients with no evidence of thrombosis or presence of the antiphospholipid syndrome was documented in this study. This link was observed, alike the general population of uveitis patients, mainly in patients with anterior eye inflammation. A possible interaction between aPL and uveitis, mediated by non-thrombotic mechanisms, requires further studies.

Type 1 Gaucher disease may be related to the presence of autoantibodies. Their clinical significance is questioned. Primary endpoint was to compare the prevalence of autoantibodies in type 1 Gaucher disease patients with healthy subjects, seeking correlations with autoimmune characteristics. Secondary endpoints were to determine whether patients with autoantibodies reported autoimmunity-related symptoms and if genotype, splenectomy or treatment influenced autoantibodies presence.
Type 1 Gaucher disease patients and healthy volunteers were included in this national multicenter exploratory study. Autoantibodies presence was compared in both groups and assessed regarding to genotype, splenectomy, Gaucher disease treatment and autoimmunity-related symptoms.
Twenty healthy subjects and 40 type 1 Gaucher disease patients were included. Of the studied group: 15 patients undergone splenectomy, 37 were treated either with enzyme replacement therapy (34) or with substrate reduction therapy (3), 25 were homozygous/heterozygous for the N370S mutation. In type 1 Gaucher disease group (studied group), 52% had positive autoantibodies versus 26% in control group. Antiphospholipid antibodies were more frequent in the studied group (30% vs. 5%), but without correlation to thrombosis, osteonecrosis or bone infarcts. In the studied group, antinuclear antibodies were more frequent (25% vs. 16%). None of the patients with autoantibodies had clinical manifestations of autoimmune diseases. Autoantibodies were not correlated with treatment, genotype, or splenectomy, except for anticardiolipid, more frequent in splenectomized patients.
In type 1 Gaucher disease, autoantibodies were more frequent compared to a healthy population. However, they were not associated with an increased prevalence of clinical active autoimmune diseases.

Non-organ-specific autoantibodies and thyroid autoantibodies have been frequently found in chronic carriers of hepatitis C virus (HCV). With respect to endomysial antibodies and tissue transglutaminase, it is controversial whether the prevalence of gluten-related seromarkers is higher in patients with HCV. In such cases, in addition to acknowledging any currently existing autoimmune disease, recognizing the risk of the patient developing an autoimmune disease during interferon (IFN)-based treatment must be a principle concern. From a clinical point-of-view, the presence of autoantibodies arouses suspicion that an autoimmune disease may be present or may be precipitated by IFN-based HCV treatment. In this paper, we review the prevalence of autoantibodies in individuals with hepatitis C, the clinical significance of these autoantibodies, and the approach recommended for such situations.

BACKGROUND: Several autoimmune diseases (ADs) can mimic multiple sclerosis (MS). For this reason, testing for auto-antibodies (auto-Abs) is often included in the diagnostic work-up of patients with a clinically isolated syndrome (CIS).
OBJECTIVE: The purpose was to study how useful it was to systematically determine antinuclear-antibodies, anti-SSA and anti-SSB in a non-selected cohort of CIS patients, regarding the identification of other ADs that could represent an alternative diagnosis.
METHODS: From a prospective CIS cohort, we selected 772 patients in which auto-Ab levels were tested within the first year from CIS. Baseline characteristics of auto-Ab positive and negative patients were compared. A retrospective revision of clinical records was then performed in the auto-Ab positive patients to identify those who developed ADs during follow-up.
RESULTS: One or more auto-Ab were present in 29.4% of patients. Only 1.8% of patients developed other ADs during a mean follow-up of 6.6 years. In none of these cases the concurrent AD was considered the cause of the CIS. In all cases the diagnosis of the AD resulted from the development of signs and/or symptoms suggestive of each disease.
CONCLUSIONS: Antinuclear-antibodies, anti-SSA and anti-SSB should not be routinely determined in CIS patients but only in those presenting symptoms suggestive of other ADs.