Lessons learned: A look back at the performance of nine COVID-19 serologic assays and their proposed utility.

Background: Serologic assays for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been proposed to assist with the acute diagnosis of infection, support epidemiological studies, identify convalescent plasma donors, and evaluate vaccine response.

Methods: We report an evaluation of nine serologic assays: Abbott (AB) and Epitope (EP) IgG and IgM, EUROIMMUN (EU) IgG and IgA, Roche anti-N (RN TOT) and anti-S (RS TOT) total antibody, and DiaSorin (DS) IgG. We evaluated 291 negative controls (NEG CTRL), 91 PCR positive (PCR POS) patients (179 samples), 126 convalescent plasma donors (CPD), 27 healthy vaccinated donors (VD), and 20 allogeneic hematopoietic stem cell transplant (HSCT) recipients (45 samples).

Evaluation of Three Commercial and Two Non-Commercial Immunoassays for the Detection of Prior Infection to SARS-CoV-2.

Background: Serological testing provides a record of prior infection with SARS-CoV-2, but assay performance requires independent assessment.

Methods: We evaluated 3 commercial (Roche Diagnostics pan-IG, and Epitope Diagnostics IgM and IgG) and 2 non-commercial (Simoa and Ragon/MGH IgG) immunoassays against 1083 unique samples that included 251 PCR-positive and 832 prepandemic samples.

Results: The Roche assay registered the highest specificity 99.

Different indirect immunofluorescence ANA substrate performance in a diagnostic setting of patients with SLE and related disorders: retrospective review and analysis.

Objective: Given the increasing relevance of the ANA assay to classification of SLE and the uncertainty and variation surrounding different ANA assay performance, we compared the human epithelial type 2 (HEp-2) to mouse liver (ML) substrate in our local cohort and provided a review of the evidence for their use in autoimmune rheumatic diseases (ARDs).

Methods: Electronic health record data (2003-2008) were used to identify patients who had concurrent HEp-2 and ML ANA, and a diagnosis of SLE or other ARDs. We determined the agreement between HEp-2 and ML ANA regarding positivity, titre and pattern, and their predictors.

A comparative study on clinical and serological characteristics between patients with rhupus and those with systemic lupus erythematosus and rheumatoid arthritis.

Background: The concomitant presence of two autoimmune diseases - systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) - in the same patient is known as rhupus. We evaluated a group of patients with rhupus to clarify further their clinical, serological and immunogenic features in a multi-centre cohort. In addition, the study aimed to explore the utility of the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) SLE classification criteria in our group of patients with rhupus.

Evaluation of two commercial and two non-commercial immunoassays for the detection of prior infection to SARS-CoV-2.

Background Seroepidemiology is an important tool to characterize the epidemiology and immunobiology of SARS-CoV-2 but many immunoassays have not been externally validated raising questions about reliability of study findings. To ensure meaningful data, particularly in a low seroprevalence population, assays need to be rigorously characterized with high specificity. Methods We evaluated two commercial (Roche Diagnostics and Epitope Diagnostics IgM/IgG) and two non-commercial (Simoa and Ragon/MGH IgG) immunoassays against 68 confirmed positive and 232 pre-pandemic negative controls.

Elevated Anti-Citrullinated Protein Antibodies Prior to Rheumatoid Arthritis Diagnosis and Risks for Chronic Obstructive Pulmonary Disease or Asthma.

Objective: To investigate elevation of anti-citrullinated protein antibodies (ACPAs) before diagnosis of rheumatoid arthritis (RA) and risks for chronic obstructive pulmonary disease (COPD) or asthma.

Methods: We performed a matched cohort study nested within the Nurses' Health Studies among women who donated blood. Women with incident RA after blood draw (self-reported, then confirmed by medical records) were each matched to 3 controls by age, cohort, year, and menopausal factors.

Asthma and elevation of anti-citrullinated protein antibodies prior to the onset of rheumatoid arthritis.

Background: Anti-citrullinated protein antibodies (ACPA) are central to rheumatoid arthritis (RA) pathogenesis and may develop at inflamed mucosa. We investigated whether asthma, a disease of airway mucosal inflammation, was associated with elevated ACPA before RA diagnosis.

Methods: We performed a nested case-control study among women in two prospective cohorts, the Nurses' Health Study (NHS; 1976-2014) and NHSII (1989-2015).

Impact of Cyclic Citrullinated Peptide Antibody Level on Progression to Rheumatoid Arthritis in Clinically Tested Cyclic Citrullinated Peptide Antibody-Positive Patients Without Rheumatoid Arthritis.

Objective: To investigate the risk of progression to rheumatoid arthritis (RA) in patients who were cyclic citrullinated peptide (CCP) antibody positive without RA at initial presentation.

Methods: We performed a retrospective cohort study of CCP+ individuals seen at a US tertiary care system between 2009 and 2018 who were without RA or other systemic rheumatic disease by medical record review at the time of CCP antibody positivity. Progression to classifiable RA was determined through medical record review.

Disease associations with isolated elevations of each of the four IgG subclasses.

Purpose: Immunoglobulin G4-related disease (IgG4-RD) is a relatively newly defined disease entity that refers to a group of immune-mediated disorders that have certain histopathologic, serologic, and clinical features in common. IgG4-RD is often associated with elevated serum IgG4. The discovery of IgG4-RD highlights the scarcity of literature examining elevations in other IgG subclasses and their potential associations to disease.

Effects of Cognitive-Behavioral Therapy (CBT) on Brain Connectivity Supporting Catastrophizing in Fibromyalgia.

Objective(s): Fibromyalgia (FM) is a chronic, common pain disorder characterized by hyperalgesia. A key mechanism by which cognitive-behavioral therapy (CBT) fosters improvement in pain outcomes is via reductions in hyperalgesia and pain-related catastrophizing, a dysfunctional set of cognitive-emotional processes. However, the neural underpinnings of these CBT effects are unclear.

Laboratory testing for the diagnosis, evaluation, and management of systemic lupus erythematosus: Still more questions for the next generations: A Tribute and Thanks and in Memory of my mentor: Henry G. Kunkel.

This paper is a review, personal memoir, a tribute to Henry Kunkel, and a critique regarding laboratory tests used for the evaluation, diagnosis, and understanding Autoimmune Rheumatic Diseases, in particular systemic lupus erythematosus (SLE).

Lupus anticoagulant testing using two parallel methods detects additional cases and predicts persistent positivity.

Background: Antiphospholipid antibody syndrome (APS) is characterized by laboratory evidence of antiphospholipid antibodies (aPL) [e.g. lupus anticoagulant (LA), anticardiolipin (ACL), and/or antiβ2-glycoprotein I (aB2GPI)] in a clinical setting of thrombosis or pregnancy morbidity.

Myeloperoxidase-antineutrophil Cytoplasmic Antibodies (MPO-ANCA) and Proteinase 3-ANCA without Immunofluorescent ANCA Found by Routine Clinical Testing.

Objective: Concurrent testing for serum antineutrophil cytoplasmic antibodies (ANCA) by indirect immunofluorescence (IF) and by antiproteinase 3 (PR3)/antimyeloperoxidase (MPO) antibody assays may identify patients with PR3-ANCA or MPO-ANCA despite a negative IF (IF-negative MPO/PR3-positive); however, the significance of this result is not clear. We sought to determine whether IF-negative, MPO/PR3-positive results identified any cases of clinically meaningful systemic vasculitis at our institution.

Methods: We conducted a retrospective chart review of all IF-negative, MPO/PR3-positive patients identified at our institution over a 2-year period.

Narcolepsy, 2009 A(H1N1) pandemic influenza, and pandemic influenza vaccinations: what is known and unknown about the neurological disorder, the role for autoimmunity, and vaccine adjuvants.

The vaccine safety surveillance system effectively detected a very rare adverse event, narcolepsy, in subjects receiving AS03-adjuvanted A(H1N1) pandemic vaccine made using the European inactivation/purification protocol. The reports of increased cases of narcolepsy in non-vaccinated subjects infected with wild A(H1N1) pandemic influenza virus suggest a role for the viral antigen(s) in disease development. However, additional investigations are needed to better understand what factor(s) in wild influenza infection trigger(s) narcolepsy in susceptible hosts.

Creation of a novel, interdisciplinary, multisite clerkship: "understanding lupus".

Few medical school electives include longitudinal patient care across clinical specialties and environments. Systemic lupus erythematosus represents a disease process with complex pathophysiology for students to learn from providers across medical fields, including dermatology, rheumatology, nephrology, and cardiology, in both pediatric and adult patients. Diagnosis, understanding, and management of lupus also rely heavily on basic science and clinical immunology, providing a link to the preclinical curriculum.

Association of discoid lupus erythematosus with other clinical manifestations among patients with systemic lupus erythematosus.

Background: Cutaneous discoid lupus erythematosus (DLE) among patients with systemic lupus erythematosus (SLE) may be associated with less severe disease and with low frequency of nephritis and end-stage renal disease (ESRD).

Objective: We sought to investigate associations between confirmed DLE and other SLE manifestations, adjusting for confounders.

Methods: We identified patients with rheumatologist confirmation, according to 1997 American College of Rheumatology (ACR) SLE classification criteria, more than 2 visits, longer than 3 months of follow-up, and documented year of SLE diagnosis.

Associations of autoantibodies, autoimmune risk alleles, and clinical diagnoses from the electronic medical records in rheumatoid arthritis cases and non-rheumatoid arthritis controls.

Objective: The significance of non-rheumatoid arthritis (RA) autoantibodies in patients with RA is unclear. The aim of this study was to assess associations of autoantibodies with autoimmune risk alleles and with clinical diagnoses from the electronic medical records (EMRs) among RA cases and non-RA controls.

Methods: Data on 1,290 RA cases and 1,236 non-RA controls of European genetic ancestry were obtained from the EMRs of 2 large academic centers.

Isolation of monoclonal antibodies with predetermined conformational epitope specificity.

Existing technologies allow isolating antigen-specific monoclonal antibodies (mAbs) from B cells. We devised a direct approach to isolate mAbs with predetermined conformational epitope specificity, using epitope mimetics (mimotopes) that reflect the three-dimensional structure of given antigen subdomains. We performed differential biopanning using bacteriophages encoding random peptide libraries and polyclonal antibodies (Abs) that had been affinity-purified with either native or denatured antigen.

To what extent can preventive treatments prevent damage from systemic lupus erythematosus?

Managing lupus patients traditionally involves treating manifestations of active disease with the most effective and least toxic therapies so that "damage" from ongoing disease or treatments can be minimized. Damage in clinical epidemiologic studies is usually defined by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, a validated, organ-specific assessment tool. This review summarizes recent developments regarding organ-specific manifestations and lupus-related damage and their prevention.

Erroneous augmentation of multiplex assay measurements in patients with rheumatoid arthritis due to heterophilic binding by serum rheumatoid factor.

Objective: Serum rheumatoid factor (RF) and other heterophilic antibodies potentially interfere with antibody-based immunoassays by nonspecifically binding detection reagents. The purpose of this study was to assess whether these factors confound multiplex-based immunoassays, which are used with increasing frequency to measure cytokine and chemokine analytes in patients with rheumatoid arthritis (RA).

Methods: We performed multiplex immunoassays using different platforms to measure analyte concentrations in RA patient samples.

Serial serum free light chain measurements do not detect changes in disease status earlier than electrophoretic M-spike measurements in patients with intact immunoglobulin myeloma.

Background: Serum free light chains (SFLC) are used to manage patients with light chain or hyposecretory myeloma, and may also be useful in patients with intact immunoglobulin myeloma (IIMM), because their shorter half-life may enable earlier indication of relapse/response than electrophoretic M-spikes or heavy chain (IgGA) immunonephelometry.

Methods: One thousand five SFLC, M-spike, and IgGA concentrations were compared at multiple time points during the treatment of 17 myeloma patients, followed over 7.7-63.