Case Report: Multicentric Reticulohistiocytosis Associated With Posterior Mediastinal Adenosquamous Carcinoma, Antinuclear Antibody Positivity and Lupus Anticoagulant Positivity

Multicentric reticulohistiocytosis (MRH) is a rare systemic disease of non-Langerhans cell histiocytosis. A number of studies in the literature have documented that it can coexist with malignancy or autoimmune disease, making it difficult to determine the most appropriate therapy. Here, we present a case study of MRH associated with posterior mediastinal adenosquamous carcinoma along with antinuclear antibody positivity and lupus anticoagulant positivity. The patient experienced 6 months of clinical benefit after surgical resection and chemoradiotherapy of the mediastinal malignancy. This case adds to the available literature on multicentric reticulohistiocytosis associated with different types of malignancy and provides supplementary clinical data on the coexistence of this syndrome with malignancy and immune system abnormalities. To the best of our knowledge, this is the first case study describing MRH accompanied by posterior mediastinal adenosquamous carcinoma and lupus anticoagulant positivity. The unknown aetiology and polymorphic clinical presentation of MRH warrants further investigation.

Measurement of antibody levels in patients with COVID-19 over time by immunofluorescence assay: a longitudinal observational study

Background During the coronavirus disease 2019 (COVID-19) pandemic, antibody screening is a critical tool to assess anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunity. We examined variation in antibody titers associated with age and sex among patients with confirmed COVID-19. Methods Blood IgG levels were tested in 1081 patients with positive SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR) tests between 1 September and 31 December 2020. Patients who did not experience reinfection were identified. Serum IgG levels were measured by immunofluorescence assay. Antibody positivity and antibody titers were analyzed according to time since infection, sex, and age. Results The mean (standard deviation) age was 41.2 (14.2) years and 41.2% of patients were women. The lowest antibody positivity rate between the first and ninth month post-infection was detected in the sixth month. The lowest antibody titers among patients aged 20 to 80 years occurred in those aged 30 to 39 years. The IgG titer was positively correlated with age in years (r = 0.125) and decades (r = 0.126). Conclusions Six months after infection, anti-SARS-CoV-2 antibody titers increased. Anti-SARS-CoV-2 antibody titers also increased with age. Immunity and pathogenicity should be investigated in addition to antibody positivity rates and antibody titers.

Comparing Rheumatology Consultation Patterns Across Telehealth Platforms and Face-to-Face Clinic in the Military Health System

ABSTRACT Objective To compare patterns of rheumatology consultations and outcomes across four different platforms in the Military Health System (MHS): face-to-face, synchronous telehealth, and two asynchronous telehealth platforms. Methods We conducted a retrospective review comparing face-to-face rheumatology consults during 2019 with teleconsultations from three virtual systems in the MHS: an asynchronous email-based system from May 2006 to Feb 2018, a web-based platform from 2014 to 2018, and synchronous telehealth consults from March 2020 to March 2021. Consults were reviewed for diagnosis, and if medical evacuation was required for consults originating OCONUS or if face-to-face follow-up was required for synchronous teleconsults. Diagnoses of interest included inflammatory arthritis, noninflammatory arthritis, crystalline arthritis, myositis, lupus, vasculitis, fibromyalgia, antibody positivity without diagnosis, symptoms without specified diagnosis, and a composite of other rheumatic diseases. Results Leading diagnoses across platforms were inflammatory arthritis, noninflammatory arthritis, and a composite of other diagnoses. Consultation modality influenced the type of cases seen. Inflammatory arthritis accounted for significantly more consults in the synchronous telehealth (38.4%) and email-based (40.9%) models than in the web-based (23.7%) and face-to-face (32.0%) models. The composite of other diagnoses was the leading diagnosis for the asynchronous web-based model (32.9%), which was significantly more than the synchronous telehealth and face-to-face consults. Synchronous models saw significantly more cases of crystalline arthritis, vasculitis, and fibromyalgia. Email-based consultations resulted in medical evacuation in 25 cases and prevented evacuation in 5. Web-based consultations prompted medical evacuation in 100 cases. In the synchronous model, face-to-face follow-up was recommended in 142 (15%) cases. Conclusions Modality of consultation influences the type of cases seen. Both synchronous and asynchronous telerheumatology models were able to answer the consult question without referral for face-to-face evaluation in 79.9-85.0% of consults, suggesting teleconsultation is a viable method to increase access to high-quality rheumatology care.

Membranous Nephropathy with Lambda Light Chain Restriction: A Rare Form with Serum Negative and Tissue Positive PLA2R Ab

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. Subepithelial polyclonal immunoglobulin deposits and >70% M-type phospholipase A2 receptor antibody positivity are typical findings in idiopathic MN. A 58-year-old female patient was admitted with clinical presentation of nephrotic syndrome. Autoimmune diseases, infections, and malignancies were ruled out after clinical and laboratory evaluations. Diagnostic work-up revealed serum PLA2R antibody negativity and diffuse thickening of glomerular capillary wall on biopsy, while glomerular capillary wall IgG, C3, and Lambda monotypic light chain deposition and PLA2R1 positivity were detected by immunofluorescence and immunohistochemical examination, respectively. Following prednisolone treatment, creatinine and proteinuria were markedly regressed. The MN cases with a light chain deposits are rare and experience regarding their treatment are insufficient.

Anti-Ro/SS-A Antibody is Associated with Worse Pulmonary Outcome and Reduced Overall Survival in Systemic Sclerosis

ABSTRACT Objective We sought to determine the association of anti-Ro/SS-A antibody with organ involvement and disease outcome, in patients with systemic sclerosis (SSc). Methods A retrospective, long-term study of a cohort of incident patients diagnosed with SSc, and continuously followed at our rheumatology clinic during 1990-2018. Results Included were 105 patients with known anti-Ro/SS-A antibody status, 92.4% female, mean age at diagnosis 52.0±15.6 years, and median follow-up 10 years; 64% were diagnosed with limited cutaneous SSc, 18% with diffuse cutaneous SSc, and 18% had SSc siné scleroderma or undetermined disease type. Anti-Ro/SS-A antibody tested positive in 21% of patients. In univariate analysis, anti-Ro/SS-A antibody-positivity was significantly associated with SSc overlap with Sjogren’s syndrome (p <0.001). Pulmonary function tests (PFT) deterioration at last encounter was significantly associated with anti-Ro/SS-A antibody-positivity. In multivariate regression for anti-Ro/SS-A antibody-positive SSc patients and disease outcome (adjusted for age>50 years, smoking, and baseline predicted forced vital capacity (pFVC) < 80%), positive anti-Ro/SS-A antibody was significantly associated with higher all-cause mortality rate (HR 5.17, CI 95% 1.18-22.67, p=0.029), and greater deterioration of pFVC defined as decrement of last available pFVC compared to first available pFVC of ≥10% (HR 3.65, CI 95% 1.07-12.38, p=0.038). Conclusions Anti-Ro/SS-A antibody is an independent risk factor for worse pulmonary outcome and higher all-cause mortality in patients with SSc, independent of SSc clinical and/or serological subtype.

Case Report: Pediatric Malignant Atrophic Papulosis With Small Bowel Perforation and Positivity of Anticardiolipin Antibody

Malignant atrophic papulosis (MAP) is a life-threatening vasculopathy affecting the skin, gastrointestinal tract, central nervous system, pleural membrane, and pericardium. MAP carries a poor prognosis primarily because of its systemic involvement. It is extremely rare in children. Herein, we report a pediatric case of MAP with small bowel perforation and anticardiolipin antibody positivity.

In-depth characterization of the serum antibody epitope repertoire in inflammatory bowel disease using phage-displayed immunoprecipitation sequencing

Inflammatory bowel diseases (IBD), e.g. Crohn's disease (CD) and ulcerative colitis (UC), are chronic immune-mediated inflammatory diseases. A comprehensive overview of an IBD-specific antibody epitope repertoire is, however, lacking. We leveraged a high-throughput phage-displayed immunoprecipitation sequencing (PhIP-seq) workflow to identify antibodies against 344,000 antimicrobial, immune and food antigens in 497 IBD patients as compared to 1,326 controls. IBD was characterized by 373 differentially abundant antibodies (202 overrepresented and 171 underrepresented), with 17% shared by both IBDs, 55% unique to CD and 28% unique to UC. Antibodies against bacterial flagellins dominated in CD and were associated with ileal involvement, fibrostenotic disease and anti-Saccharomyces cerevisiae antibody positivity, but not with fecal microbiome composition. Antibody epitope repertoires accurately discriminated CD from controls (AUC=0.89), and similar discrimination was achieved when using only ten antibodies (AUC=0.87). IBD patients thus show a distinct antibody repertoire against selected peptides, allowing patient stratification and discovery of immunological targets.

Prevalence and Genetic Analysis of Porcine Circovirus 3 in China From 2019 to 2020

Porcine circovirus type 3 (PCV3), a virus belonging to the Circoviridae family, is considered to be associated with respiratory and neurological signs, cardiac and multisystemic inflammation, reproductive failure, and porcine dermatitis and nephropathy syndrome-like disease in pigs (Sus scrofa). In this study, epidemiological and serological investigations of PCV3 in clinically healthy pigs from different regions of China were performed. Overall, 42.87% (1,101/2,568) of pigs were positive for PCV3 Cap antibody via indirect enzyme-linked immunosorbent assay, with a higher prevalence of PCV3 in multiparous sows (62.22%, 881/1,416) and fattening pigs (28.96%, 159/549) than in suckling piglets (8.96%, 32/357) and nursery pigs (11.79%, 29/246). Of the 2,568 samples, 255 were further tested for PCV3 DNA using real-time polymerase chain reaction, and 63.14% of these were positive, with nearly half having <10 virus copies. The PCV3 DNA and antibody positivity rates were high in the pig serum samples; however, the virus titers and antibody levels were both low, indicating that the humoral immune response of PCV3-infected pigs was weak or lagging, and persistent or repeated infections could occur. Additionally, the complete genomes of 23 PCV3 strains were sequenced and analyzed, which showed nucleotide identities of 98.5~100.0%, 98.6~100.0%, and 99.2~100.0% in the complete genome, open reading frame (ORF)2, and ORF1 sequences, respectively, and amino acid identities of 96.7~100.0% and 99.3~100.0% in the capsid and replicase proteins, respectively. Phylogenetic analysis based on ORF2 nucleotide sequences indicated that the PCV3 strains obtained in the present study could be classified into three sub-clades, with most strains clustered into clade 3c, indicating that PCV3c is the dominant subtype in the regions of China investigated. In general, the present study revealed a high prevalence and high genetic divergence of PCV3 among Chinese pig herds, and indicated that the potential effect of PCV3 on the pig industry may be a concern.

Audiological Involvement in Patients with Systemic Sclerosis

Objective The aim of the present study was to evaluate hearing loss in patients diagnosed with SSc (systemic sclerosis) and to investigate the relation between hearing loss, subtypes of the disease, its duration and clinical findings, and antibody positivity. Methods The study included 47 patients with SSc and 44 healthy controls. Audiometric, tympanometric and otoacoustic emission measurements were applied to both groups. Results The evaluation of the participants medical history showed that among the patients with SSc, 19.1% experienced ear fullness, 27.7% experienced vertigo and 36.2% experienced tinnitus. Hearing loss was detected in 23.4% of the patients with SSc. The corresponding result was 4.3% in the control group with a statistically significant difference (p = 0.001). Transient evoked otoacoustic emission (TEOAE) amplitude values were significantly lower in the patients both ears with SSc than the control group (p < 0.005). Duration of disease was significantly longer and DLCO (diffusing capacity of the lungs for carbon monoxide) values were significantly higher in the patients with SSc and sensorineural hearing loss. Conclusions The present study found that the incidence of hearing loss was significantly higher in the study group than healthy control group. In addition to other organ involvements, cochlear involvement occurs in these patients, and further studies are required.