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).

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.

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.

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.

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.

ANA screening: an old test with new recommendations.

The impact of autoimmune diseases is growing from both a clinical and a laboratory point of view. Diagnostic assays are now being transferred from dedicated specialised laboratories into high-throughput service laboratories. The increasing number of available methods has raised the variability among the laboratories, making their reproducibility a critical problem.

Association of measles virus with rheumatoid arthritis.

Objective: Rheumatoid arthritis (RA) is a chronic inflammatory polyarthritis; while the cause is unknown, it has been speculated that an infectious agent could be the trigger for the disease. Numerous attempts at isolating an agent have been unsuccessful. Our purpose was to identify a virus from diseased tissue from a patient with RA.

Autoantibodies to tumor necrosis factor in patients with rheumatoid arthritis and systemic lupus erythematosus.

Objective: To detect autoantibodies to tumor necrosis factor (TNF) in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), and to determine their clinical correlates.

Methods: Ninety-two patients with RA and 62 with SLE were studied. Sera were examined for autoantibodies to TNF by enzyme linked immunoassay.

Comparison of threshold cutpoints and continuous measures of anti-cyclic citrullinated peptide antibodies in predicting future rheumatoid arthritis.

Objective: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are strongly associated with increased risk of rheumatoid arthritis (RA).While the anti-CCP level is commonly dichotomized for clinical use, the best threshold for and utility of the titer as a continuous variable to predict development of RA are uncertain.

Methods: Using data from the Nurses' Health Study and Nurses' Health Study II longitudinal cohorts, we examined the sensitivity, specificity, and hazard of RA at various thresholds of the anti-CCP.

C-reactive protein, anti-C-reactive protein antibodies and clinical atherosclerosis.

There has been considerable interest in the relationship between C-reactive protein (CRP) and atherosclerosis. We have previously demonstrated that individuals, especially those with rheumatoid arthritis and systemic lupus erythematosus, may produce antibodies to CRP. This study was therefore undertaken to determine the possible association between anti-CRP antibodies and atherosclerosis.

Barriers to a trial of atherosclerosis prevention in systemic lupus erythematosus.

Objective: The effectiveness of aggressive management of traditional risk factors for accelerated atherosclerosis in systemic lupus erythematosus (SLE) has been advocated but not proven. We conducted a pilot, randomized, controlled trial of known prevention medications (pravastatin, ramipril, aspirin, and a combination B vitamin) plus individualized cardiovascular prevention education. We describe our experience in recruiting and retaining patients with SLE in this trial.