Case Report: Multicentric Reticulohistiocytosis Associated With Posterior Mediastinal Adenosquamous Carcinoma, Antinuclear Antibody Positivity and Lupus Anticoagulant Positivity.
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SUBMITTER: Tang Z
PROVIDER: S-EPMC8777097 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveThe spectrum of antinuclear antibodies (ANAs) is changing to include both nuclear staining as well as cytoplasmic and mitotic cell patterns (CMPs) and accordingly a change is occurring in terminology to anticellular antibodies. This study examined the prevalence of indirect immunofluorescence (IIF) anticellular antibody staining using the Systemic Lupus International Collaborating Clinics inception cohort.MethodsAnticellular antibodies were detected by IIF on HEp-2000 substrate using the baseline serum. Three serologic subsets were examined: ANA positive (presence of either nuclear or mixed nuclear/CMP staining), anticellular antibody negative (absence of any intracellular staining), and isolated CMP staining. The odds of being anticellular antibody negative versus ANA or isolated CMP positive was assessed by multivariable analysis.ResultsA total of 1,137 patients were included; 1,049 (92.3%) were ANA positive, 71 (6.2%) were anticellular antibody negative, and 17 (1.5%) had an isolated CMP. The isolated CMP-positive group did not differ from the ANA-positive or anticellular antibody-negative groups in clinical, demographic, or serologic features. Patients who were older (odds ratio [OR] 1.02 [95% confidence interval (95% CI) 1.00, 1.04]), of white race/ethnicity (OR 3.53 [95% CI 1.77, 7.03]), or receiving high-dose glucocorticoids at or prior to enrollment (OR 2.39 [95% CI 1.39, 4.12]) were more likely to be anticellular antibody negative. Patients on immunosuppressants (OR 0.35 [95% CI 0.19, 0.64]) or with anti-SSA/Ro 60 (OR 0.41 [95% CI 0.23, 0.74]) or anti-U1 RNP (OR 0.43 [95% CI 0.20, 0.93]) were less likely to be anticellular antibody negative.ConclusionIn newly diagnosed systemic lupus erythematosus, 6.2% of patients were anticellular antibody negative, and 1.5% had an isolated CMP. The prevalence of anticellular antibody-negative systemic lupus erythematosus will likely decrease as emerging nomenclature guidelines recommend that non-nuclear patterns should also be reported as a positive ANA.
| S-EPMC7268889 | biostudies-literature
Project description:ObjectivesFollowing up the systemic lupus erythematosus (SLE) genome-wide association studies (GWAS) identification of NMNAT2 at rs2022013, we fine-mapped its 150 kb flanking regions containing NMNAT2 and SMG7 in a 15 292 case-control multi-ancestry population and tested functions of identified variants.MethodsWe performed genotyping using custom array, imputation by IMPUTE 2.1.2 and allele specific functions using quantitative real-time PCR and luciferase reporter transfections. SLE peripheral blood mononuclear cells (PBMCs) were cultured with small interfering RNAs to measure antinuclear antibody (ANA) and cyto/chemokine levels in supernatants using ELISA.ResultsWe confirmed association at NMNAT2 in European American (EA) and Amerindian/Hispanic ancestries, and identified independent signal at SMG7 tagged by rs2702178 in EA only (p=2.4×10-8, OR=1.23 (95% CI 1.14 to 1.32)). In complete linkage disequilibrium with rs2702178, rs2275675 in the promoter region robustly associated with SMG7 mRNA levels in multiple expression quantitative trait locus (eQTL) datasets. Its risk allele was dose-dependently associated with decreased SMG7 mRNA levels in PBMCs of 86 patients with SLE and 119 controls (p=1.1×10-3 and 6.8×10-8, respectively) and conferred reduced transcription activity in transfected HEK-293 (human embryonic kidney cell line) and Raji cells (p=0.0035 and 0.0037, respectively). As a critical component in the nonsense-mediated mRNA decay pathway, SMG7 could regulate autoantigens including ribonucleoprotein (RNP) and Smith (Sm). We showed SMG7 mRNA levels in PBMCs correlated inversely with ANA titres of patients with SLE (r=-0.31, p=0.01), and SMG7 knockdown increased levels of ANA IgG and chemokine (C-C motif) ligand 19 in SLE PBMCs (p=2.0×10-5 and 2.0×10-4, respectively).ConclusionWe confirmed NMNAT2 and identified independent SMG7 association with SLE. The inverse relationship between levels of the risk allele-associated SMG7 mRNAs and ANA suggested the novel contribution of mRNA surveillance pathway to SLE pathogenesis.
| S-EPMC4949149 | biostudies-literature
Project description:Age-associated increases in antinuclear antibodies (ANA) in the general population are commonly noted but the mechanisms underlying this observation are unclear. This study aims to evaluate whether shorter peripheral blood mononuclear cell (PBMC) telomere length, a marker of more advanced biological age, is associated with ANA positivity prevalence and incidence in middle and older aged autoimmune disease-free individuals from the Baltimore Longitudinal Study of Aging (BLSA). Telomere length was measured by Southern Blot and categorized into tertiles. ANA was measured in a 1:80 and a 1:160 dilution of sera by immunofluorescence using HEp-2?cells (seropositive?=?3 or 4). Multiple logistic regression was used to estimate the odds ratios and 95% confidence intervals of ANA positivity comparing the shorter tertiles of telomere length to the longest tertile for two cross-sectional points in time and then longitudinally to assess the association between shorter telomere length and incident ANA positivity. Cross-sectional analyses were adjusted for sex, race and BMI (N?=?368 baseline, N?=?370 follow-up) and longitudinal analyses were adjusted for sex, race, BMI and time between baseline and follow-up (N?=?246). No statistically significant cross-sectional associations were observed at baseline or follow-up. Among those where ANA negative at baseline, individuals with shorter telomeres were more likely to be ANA positive at follow-up, an average 13 years later. Individuals with short telomeres at both time periods were more likely to be ANA positive. Findings suggest that ANA positivity in the general population may be indicative of immune dysfunction resulting from advanced cellular aging processes.
| S-EPMC6878149 | biostudies-literature
Project description:IntroductionThe aim of the study was to determine whether Olf1/EBF associated zinc finger protein (OAZ), a transcription factor encoded by a positional systemic lupus erythematosus (SLE) candidate gene, plays a functional role in the pathogenesis in SLE.MethodsGene expression levels in peripheral blood cells (PBLs) measured using quantitative real-time polymerase chain reaction (qPCR) were assessed for association with disease activity and the presence of specific autoantibodies. Peripheral blood mononuclear cells (PBMCs) were incubated with specific siRNAs for three days, then cells were harvested for measuring mRNA levels using qPCR, and supernatants for levels of total immunoglobulin (Ig)G and IgM as well as secreted cytokines, chemokine and antinuclear antibodies (ANA) using ELISA. Indirect immunofluorescence was also applied for ANA detection.ResultsOAZ gene expressions in PBLs from 40 ANA-positive SLE patients were significantly increased than those from 30 normal controls (P < 0.0001) and 18 patients with rheumatoid arthritis (P < 0.01). In SLE patients, OAZ transcripts were positively correlated with SLE disease activity index (SLEDAI) score (r = 0.72, P < 0.0001) and higher in those positive for anti-dsDNA or anti-Sm antibodies (both P < 0.05). Co-culturing with OAZ siRNAs reduced mRNA levels of OAZ by 74.6 +/- 6.4% as compared to those co-cultured with non-targeting siRNA and OAZ silencing resulted in reduced total IgG, ANA, interferon (IFN)-gamma, interleukin (IL)-10, IL-12 and IL-21, but elevated CCL2 levels in culture supernatants (P < 0.05). The declined ANA levels correlated with inhibited OAZ expression (r = 0.88, P = 0.05), reduced IL-21 levels (r = 0.99, P < 0.01), and elevated chemokine (C-C motif) ligand 2 levels (r = -0.98, P < 0.01). Expressions of ID1-3 were significantly down-regulated by 68.7%, 70.2% and 67.7% respectively after OAZ silence, while ID3 was also highly expressed in SLE PBLs (P < 0.0001) and associated with disease activity (r = 0.76, P < 0.0001) as well as anti-dsDNA or anti-Sm antibodies (both P < 0.05).ConclusionsElevated expression of OAZ transcripts in SLE PBLs were strongly correlated with disease activity. Suppression of OAZ expression inhibited downstream ID levels, and secretion of ANA and IL-21, implicating a role of OAZ pathway in the pathogenesis of SLE.
| S-EPMC2888210 | biostudies-literature
Project description:Antinuclear antibody (ANA) analysis by immunofluorescence (IF) microscopy remains a diagnostic hallmark of systemic lupus erythematosus (SLE). The clinical relevance of ANA fine-specificities in SLE has been addressed repeatedly, whereas studies on IF-ANA staining patterns in relation to disease manifestations are very scarce. This study was performed to elucidate whether different staining patterns associate with distinct SLE phenotypes.Observational cohort study.One university hospital rheumatology unit in Sweden.The study population consisted of 222 cases (89% women; 93% Caucasians), where of 178 met ?4/11 of the 1982 American College of Rheumatology (ACR-82) criteria. The remaining 20% had an SLE diagnosis based on positive IF-ANA (HEp-2 cells) and ?2 typical organ manifestations at the time of diagnosis (Fries' criteria).The IF-ANA staining patterns homogenous (H-ANA), speckled (S-ANA), combined homogenous and speckled (HS-ANA), centromeric (C-ANA), nucleolar (N-ANA)±other patterns and other nuclear patterns (oANA) were related to disease manifestations and laboratory measures. Antigen-specificities were also considered regarding double-stranded DNA (Crithidia luciliae) and the following extractable nuclear antigens: Ro/SSA, La/SSB, Smith antigen (Sm), small nuclear RNP (snRNP), Scl-70 and Jo-1 (immunodiffusion and/or line-blot technique).54% of the patients with SLE displayed H-ANA, 22% S-ANA, 11% HS-ANA, 9% N-ANA, 1% C-ANA, 2% oANA and 1% were never IF-ANA positive. Staining patterns among patients meeting Fries' criteria alone did not differ from those fulfilling ACR-82. H-ANA was significantly associated with the 10th criterion according to ACR-82 ('immunological disorder'). S-ANA was inversely associated with arthritis, 'immunological disorder' and signs of organ damage.H-ANA is the dominant IF-ANA pattern among Swedish patients with SLE, and was found to associate with 'immunological disorder' according to ACR-82. The second most common pattern, S-ANA, associated negatively with arthritis and organ damage.
| S-EPMC3808756 | biostudies-literature
Project description:A 28-year-old female patient was hospitalized primarily because of "intermittent fever for 28 days aggravated by systemic rashes, oral ulcer, and edema in both eyelids for 5 days." During treatment, convulsions and loss of consciousness occurred. Magnetic resonance imaging (MRI) of the head revealed an abnormal signal with shadows in the bilateral frontal, parietal, temporal, and occipital lobes; cerebellar hemispheres; and basal nodes, with high signal intensity on T2 weighted imaging (T2WI), on fluid-attenuated inversion-recovery, and of the apparent diffusion coefficient and low signal intensity on T1WI and diffusion weighted imaging. Therefore, the patient was diagnosed with systemic lupus erythematosus (SLE) with reversible posterior encephalopathy syndrome (RPES). Intravenous high-dose methylprednisolone and cyclophosphamide were administered for blood pressure control, which effectively controlled the disease. Therefore, when patients with SLE and hypertension or renal insufficiency or those receiving high-dose methylprednisolone or immunosuppressants suddenly present with neurologic abnormalities, a diagnosis of RPES must be considered, and head MRI is the first choice for diagnosis of this disease. In terms of treatment, the blood pressure should be quickly controlled, and the primary disease should be aggressively treated.
| S-EPMC8326631 | biostudies-literature
Project description:Gastric adenosquamous carcinoma (GASC) is a rare variant of gastric cancer; the limited data available suggest that these tumors are more aggressive and have a worse outcome in comparison to gastric adenocarcinoma. Currently, the management of GASC is similar to adenocarcinoma. We report a case of GASC that progressed rapidly despite treatment.
| S-EPMC7433371 | biostudies-literature
Project description:ObjectiveThe clinical relevance of antiphospholipid antibodies (aPLs) in COVID-19 is controversial. This study was undertaken to investigate the prevalence and prognostic value of conventional and nonconventional aPLs in patients with COVID-19.MethodsThis was a multicenter, prospective observational study in a French cohort of patients hospitalized with suspected COVID-19.ResultsTwo hundred forty-nine patients were hospitalized with suspected COVID-19, in whom COVID-19 was confirmed in 154 and not confirmed in 95. We found a significant increase in lupus anticoagulant (LAC) positivity among patients with COVID-19 compared to patients without COVID-19 (60.9% versus 23.7%; P < 0.001), while prevalence of conventional aPLs (IgG and IgM anti-β2 -glycoprotein I and IgG and IgM anticardiolipin isotypes) and nonconventional aPLs (IgA isotype of anticardiolipin, IgA isotype of anti-β2 -glycoprotein I, IgG and IgM isotypes of anti-phosphatidylserine/prothrombin, and IgG and IgM isotypes of antiprothrombin) was low in both groups. Patients with COVID-19 who were positive for LAC, as compared to patients with COVID-19 who were negative for LAC, had higher levels of fibrinogen (median 6.0 gm/liter [interquartile range 5.0-7.0] versus 5.3 gm/liter [interquartile range 4.3-6.4]; P = 0.028) and C-reactive protein (CRP) (median 115.5 mg/liter [interquartile range 66.0-204.8] versus 91.8 mg/liter [interquartile range 27.0-155.1]; P = 0.019). Univariate analysis did not show any association between LAC positivity and higher risks of venous thromboembolism (VTE) (odds ratio 1.02 [95% confidence interval 0.44-2.43], P = 0.95) or in-hospital mortality (odds ratio 1.80 [95% confidence interval 0.70-5.05], P = 0.24). With and without adjustment for CRP level, age, and sex, Kaplan-Meier survival curves according to LAC positivity confirmed the absence of an association with VTE or in-hospital mortality (unadjusted P = 0.64 and P = 0.26, respectively; adjusted hazard ratio 1.13 [95% confidence interval 0.48-2.60] and 1.80 [95% confidence interval 0.67-5.01], respectively).ConclusionPatients with COVID-19 have an increased prevalence of LAC positivity associated with biologic markers of inflammation. However, LAC positivity at the time of hospital admission is not associated with VTE risk and/or in-hospital mortality.
| S-EPMC8250965 | biostudies-literature
Project description:Introduction Ganglioneuroma (GN) is a rare benign tumor of ganglion cell origin and can occur anywhere along the sympathetic chain. These tumors can grow to a significant size without any symptoms unless they exert a mass effect on the region they grow and start showing symptoms. Spinal extensions are rare and they may produce neurological symptoms warranting further investigation. Case presentation We described a case of posterior mediastinal ganglioneuroma in a 4-year-old boy with cervical extension who presented with quadriparesis. The radiological scan revealed large ganglioneuroma having an intradural extramedullary extension with a large posterior mediastinal component compressing and displacing the surrounding structures. He underwent consecutive surgeries for complete excision of the tumor following which he regained his power in his upper and lower limbs over the period of 2 months. Conclusion Para spinal mass with consistent radiological features suggests ganglioneuroma but confirmation should be done with biopsy. Complete excision of the tumor is the treatment of choice with close follow-up for clinical improvement and recurrence. Highlights • Ganglioneuroma is a rare neurogenic tumor that arises from the neural crest cells of the sympathetic ganglia.• A multidisciplinary team approach should be used to plan the tumor's complete excision.• Resection of the tumor is curative since these tumors are seldom malignant and have a low recurrence rate.
| S-EPMC9793127 | biostudies-literature
Project description:Antinuclear antibodies (ANA), a marker of self-reactivity to DNA and other nuclear antigens, are present in several autoimmune diseases and have been observed in healthy persons in the absence of autoimmune disease. ANA prevalence is higher in women and older adults, but the health implications of ANA in middle- to older-aged adults are unknown. Immune system differences by sex may further result in sex-specific susceptibility to morbidity. In a cross-sectional analysis of data from the Baltimore Longitudinal Study of Aging, we examined the sex-specific relationship between age and ANA as well as the associations (odds ratios and 95% confidence intervals) between ANA and type-2 diabetes and multimorbidity (2 or more chronic diseases), stratified by sex and controlling for age and race. ANA was measured in a 1:160 dilution of sera by immunofluorescence using HEp-2 cells (seropositive = 3 or 4). Overall ANA seroprevalence was 12% (15.1% in women, 8.8% in men). We observed a non-linear relationship between age and ANA that varied by sex (interaction p-value < 0.05), with a clear sex differences in younger participants (ages 48-59), which converged in the oldest (age 80+). ANA positive women had higher odds of type 2 diabetes (OR: 2.06, 95% confidence interval: 1.04, 4.07) and multimorbidity (OR: 2.47, 95% confidence interval 1.11, 5.50) than women who were ANA negative. No statistically significant associations were observed in men. Insight into differences in age-related ANA positivity and ANA associations with chronic diseases by sex is important for understanding the impact of immune dysregulation in aging individuals.
| S-EPMC7180125 | biostudies-literature