Antibodies to histone in the pediatric population: a retrospective chart review

All charts from the Cardinal Glennon Children’s Hospital Pediatric Rheumatology clinic from 1/1/2016 to 12/31/2019 with positive anti-histone antibody tests were reviewed. Frequently, these were evaluations for possible systemic lupus erythematosus or inflammatory arthritis with positive ANA testing. In addition to the anti-histone antibody titer, age, diagnostic codes, and the presence of ANA, anti DS-DNA, chromatin, SSA, SSB, Sm and RNP antibodies were recorded. In the instances where multiple auto-antibody profiles were available, the most recent was used. Charts were manually reviewed for the treating Rheumatologist’s most recent diagnosis which was recorded and used for statistical analysis. In the case of multiple diagnoses, each relevant diagnosis was recorded. Patients were allowed to have more than one diagnosis. Patients whose charts specifically noted being on medications associated with DILE, but did not have clinical manifestations were considered as possible drug induced autoantibody formation and not DILE.

Diagnoses were also grouped into the category of rheumatologic diagnoses and autoimmune diagnoses. Rheumatologic diagnoses were defined as SLE, Sjogren’s syndrome, chronic recurrent multifocal osteomyelitis(CRMO), inflammatory bowel disease(IBD)/IBD arthritis, Behcet’s, rheumatoid arthritis, JIA(all subtypes except systemic), systemic JIA, DILE, uveitis, psoriasis/psoriatic arthritis, undifferentiated connective tissue disease, inflammatory myopathy, linear scleroderma(LS) and Henoch Schonlein Purpura. Autoimmune diagnoses were defined as autoimmune hepatitis, autoimmune thyroid disease, celiac disease and type 1 diabetes in addition to the previously mentioned rheumatologic diagnoses. This was done to allow calculation of a positive predictive value for a positive anti-histone antibody test in reference to any autoimmune or rheumatologic disease given the low incidence of specific diagnoses observed in the population.

Weakly positive anti-histone titers were defined as a level from 1.0 to 1.5 units. Moderate titers were defined as 1.6–2.5 units and strongly positive titers defined as greater than 2.5 units in accordance with how results are reported back to the clinician from LabCorp. These are the standard cut-offs used by LabCorp. Anti-Histone antibody tests were performed by LabCorp using an IgG class ELISA test. Data regarding individual histone subtypes is not performed by LabCorp and was not available regarding the patients included in this study.

Positive predictive value was calculated for SLE, JIA(non-systemic), DILE, and any rheumatologic or autoimmune diagnosis. This calculation was made using the standard formula for positive predictive value (true positives divided by total positive tests [true positive plus false positive]). The clinical diagnosis (if present) from chart review was considered a true positive for purposes of calculating positive predictive value. This was then divided by the number of total positive anti-histone antibody titers within each specific subset analyzed. Subsets included patients with positive anti-histone antibodies in conjunction with other autoantibodies, along with patients with low titer anti-histone antibodies and negative ANA testing without other autoantibodies present.

A basic 2 × 2 Chi-square calculation was used to compare weak, moderate, and strong titers of antihistone antibodies in regards to the frequency of autoimmune disease in general and SLE. Specifically, weak titer was compared to moderate titer, moderate titer compared to high titer and weak titer compared to high titer.

This study was approved by the Saint Louis University Institutional Review Board, protocol #30,713.

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