In 1982, the Diagnostic and Therapeutic Criteria Committee of the American College of Rheumatology (ACR)published revised criteria for the classification of systemiclupus erythematosus (SLE) (1). During the ensuing decade several investigators, including Drs. Graham Hughes and Donato Alarcon-Segovia, among others, have described the presence and clinical associations or antiphospholipid antibodies in patients with SLE, as well as the occurrence of theprimary antiphospholipid syndrome (2-5). In 1992, Piette and colleagues suggested that the ACR revised criteria be reevaluated in light of the above discoveries (6).

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.1780400928

Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1529-0131%28199907%2942%3A7%3C1309%3A%3AAID-ANR1%3E3.0.CO%3B2-F

International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop.

Background Although much is known about the natural history of systemic lupus erythematosus (SLE), the development of SLE autoantibodies before the diagnosis of the disease has not been extensively explored. We investigated the onset and progression of autoantibody development before the clinical diagnosis. Methods The Department of Defense Serum Repository contains approximately 30 million specimens prospectively collected from more than 5 million U.S. Armed Forces personnel. We evaluated serum samples obtained from 130 persons before they received a diagnosis of SLE, along with samples from matched controls. Results In 115 of the 130 patients with SLE (88 percent), at least one SLE autoantibody tested was present before the diagnosis (up to 9.4 years earlier; mean, 3.3 years). Antinuclear antibodies were present in 78 percent (at a dilution of 1:120 or more), anti–double-stranded DNA antibodies in 55 percent, anti-Ro antibodies in 47 percent, anti-La antibodies in 34 percent, anti-Sm antibodies in 32 pe...

/pdf/development-of-autoantibodies-before-the-clinical-onset-of-43jvoafneg.pdf

Development of autoantibodies before the clinical onset of systemic lupus erythematosus.

OBJECTIVE\nTo develop a standardized nomenclature system for the neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE).\n\n\nMETHODS\nAn international, multidisciplinary committee representing rheumatology, neurology, psychiatry, neuropsychology, and hematology developed case definitions, reporting standards, and diagnostic testing recommendations. Before and after the meeting, clinician committee members assigned diagnoses to sets of vignettes randomly generated from a pool of 108 NPSLE patients. To assess whether the nomenclature system improved diagnostic agreement, a consensus index was developed and pre- and postmeeting scores were compared by t-tests.\n\n\nRESULTS\nCase definitions including diagnostic criteria, important exclusions, and methods of ascertainment were developed for 19 NPSLE syndromes. Recommendations for standard reporting requirements, minimum laboratory evaluation, and imaging techniques were formulated. A short neuropsychological test battery for the diagnosis of cognitive deficits was proposed. In the postmeeting exercise, a statistically significant improvement in diagnostic agreement was observed.\n\n\nCONCLUSION\nThe American College of Rheumatology (ACR) Nomenclature for NPSLE provides case definitions for 19 neuropsychiatric syndromes seen in SLE, with reporting standards and recommendations for laboratory and imaging tests. It is intended to facilitate and enhance clinical research, particularly multicenter studies, and reporting. In clinical settings, consultation with other specialists may be required. It should be useful for didactic purposes but should not be used uncritically or as a substitute for a clinical diagnosis. The complete case definitions are available on the ACR World Wide Web site: http://www.rheumatology .org/ar/ar.html.

The American College of Rheumatology nomenclature and case definitions for neuropsychiatric lupus syndromes

Objective. To analyze the clinical and immunologic manifestations of antiphospholipid syndrome (APS) in a large cohort of patients and to define patterns of disease expression. Methods. The clinical and serologic features of APS (Sapporo preliminary criteria) in 1,000 patients from 13 European countries were analyzed using a computerized database. Results. The cohort consisted of 820 female patients (82.0%) and 180 male patients (18.0%) with a mean +/- SD age of 42 +/- 14 years at study entry. "Primary" APS was present in 53.1% of the patients; APS was associated with systemic lupus erythematosus (SLE) in 36.2%, with lupus-like syndrome in 5.0%, and with other diseases in 5.9%. A variety of thrombotic manifestations affecting the majority of organs were recorded. A catastrophic APS occurred in 0.8% of the patients. Patients with APS associated with SLE had more episodes of arthritis and livedo reticularis, and more frequently exhibited thrombocytopenia and leukopenia. Female patients had a higher frequency of arthritis, livedo reticularis, and migraine. Male patients had a higher frequency of myocardial infarction, epilepsy, and arterial thrombosis in the lower legs and feet. In 28 patients (2.8%), disease onset occurred before age 15; these patients had more episodes of chorea and jugular vein thrombosis than the remaining patients. In 127 patients (12.7%), disease onset occurred after age 50; most of these patients were men. These patients had a higher frequency of stroke and angina pectoris, but a lower frequency of livedo reticularis, than the remaining patients. Conclusion. APS may affect any organ of the body and display a broad spectrum of manifestations. An association with SLE, the patient's sex, and the patient's age at disease onset can modify the disease expression and define specific subsets of APS.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.10187

Antiphospholipid syndrome: Clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients

Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus

The anticardiolipin syndrome

Thirty laboratories from institutions in Britain, France, Italy, The Netherlands, New Zealand, Sweden and the USA participated in a workshop to evaluate the anti-cardiolipin (aCL) test. Participants were asked to measure IgG and IgM aCL in seven samples on each of three separate days. The seven samples were prepared so that IgG and IgM aCL concentrations were known before distribution. Twenty-three of 30 laboratories measuring IgG aCL had significant regression slopes (P less than 0.001) when optical absorbance readings or counts per minute were compared with IgG aCL concentration. Twenty-four of 28 laboratories measuring IgM aCL had significant regression slopes (P less than 0.001). Coefficient of determination (R2) ranged from 81.1% to 98.7% for laboratories with valid IgG aCL assays and from 48.0% to 96.7% for valid IgM aCL assays. Valid assays had in common the use of 10% fetal calf or 10% adult bovine serum in PBS. Assays that were not valid had in common the use of PBS, PBS-Tween, or 0.3% gelatin as diluents. All laboratories with valid assays defined samples with high and moderate aCL levels as positive but there was no consensus about low positive samples. This study shows that properly performed ELISA or SRIA assays can be used to provide an accurate, reproducible, and quantitative measure of IgG and IgM aCL concentration in serum samples.

Evaluation of the anti-cardiolipin antibody test: report of an international workshop held 4 April 1986.

Quantitative isotype specific enzyme linked immunosorbent assay (ELISA) was used to determine the distribution of immunoglobulin isotypes and phospholipid specificities of anticardiolipin (anti-CL) antibodies in 40 patients with one or more of the following 'antiphospholipid (anti-PL) antibody associated clinical complications'--namely, thrombosis, fetal loss, thrombocytopenia. Twelve of 40 patients had IgG, IgM, and IgA anti-CL antibodies. Ten patients had IgG and IgM, five patients had IgG and IgA, and three patients had IgM and IgA anti-CL antibodies. There was no statistical association between any single isotype or any group of isotypes with thrombosis, fetal loss, or thrombocytopenia. The presence of IgG anti-CL antibodies in 36 of the 40 patients suggests that this isotype may be most important in determining clinical complications, but there were four patients without IgG anti-CL antibodies who also appeared susceptible to thrombosis, fetal loss, and thrombocytopenia. IgG, IgM, and IgA anti-CL antibodies bound the negatively charged phospholipids, phosphatidylserine and phosphatidylinositol, but not the zwitterionic phospholipid, phosphatidylcholine. There was no significant difference between binding to cardiolipin and binding to other negatively charged phospholipids, suggesting that the specificity of these antibodies is for negatively charged phospholipids in general rather than for cardiolipin in particular.

https://ard.bmj.com/content/annrheumdis/46/1/1.full.pdf

Anticardiolipin antibodies: isotype distribution and phospholipid specificity.

Antiphospholipid Syndrome most commonly comes to attention in a diagnostic work-up for patients with recurrent pregnancy loss. Repetitive Pregnancy Loss is defined as combination of pregnancy losses, often involving three consecutive first trimester losses or a single second trimester loss. Just 2 percent of pregnant women experience two consecutive pregnancy losses and only 0.4 to 1 percent have three consecutive pregnancy losses 1 . In a patient’s first pregnancy, the risk of miscarriage is 11 to 13 percent 2 . After one miscarriage, the likelihood of subsequent loss increases to 14 to 21 percent. After two or three miscarriages, the rate is 24 to 29 percent and 31 to 33 percent, respectively. The same relationship holds true for pregnancy losses later in pregnancy 3 . Anti-Phospholipid Antibody Syndrome is the best understood mechanism for recurrent pregnancy loss 4 .

A. E. Gharavi

Papers

Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus

The anticardiolipin syndrome

Evaluation of the anti-cardiolipin antibody test: report of an international workshop held 4 April 1986.

Anticardiolipin antibodies: isotype distribution and phospholipid specificity.

Anti-phospholipid antibodies.