The immunologic features of patients with early-onset and polyautoimmunity

Abstract

Inflammatory conditions are increasingly described in patients with primary immunodeficiencies; however, little is known about the prevalence of immune defects in patients who present first with autoimmunity. We describe the immunologic features of children with early-onset/polyautoimmunity followed in the Multiple Autoimmunity and Immunodeficiency (MAID) Clinic, where patients are co-managed by rheumatologists and immunologists. The most common autoimmune manifestations were cytopenias, lymphoproliferation, and colitis. Recurrent infections were noted in 65% of patients. Abnormalities in lymphocyte subsets and immunoglobulins were common. A pathogenic variant was identified in 19% of patients, and 2 novel inherited disorders were discovered. Additionally, 42% of patients had treatment changes implemented in the MAID clinic. By evaluating this unique cohort of patients, we report on the immunologic underpinning of early-onset/polyautoimmunity. The high rate of genetic diagnoses and treatment interventions in this population highlights the value of collaboration between rheumatologists and immunologists in the care of these complex patients.

Keywords: Autoimmunity; Immune dysregulation; Primary immunodeficiency.

Figure 1.. Age Distribution of Patients in the MAID Clinic.

The graph depicts the ages of patients at initial presentation to the MAID clinic. MAID, Multiple Autoimmunity and Immunodeficiency Clinic

Figure 2.. Autoimmune Manifestations of Patients in the MAID Clinic.

A) The percentage of patients in the MAID clinic with each autoimmune manifestation is depicted in the graph. B) Forty-five patients had cytopenias, and the total number of patients with each affected cell line is depicted. C) Thirty-three patients had lymphoproliferation, and the number of patients with LAD and HSM is depicted. D) Thirty-three patients had GI involvement, and the number of patients with the most frequent types of GI manifestations is depicted. E) The percentage of patients in the MAID clinic with each autoantibody is depicted in the graph. MAID, Multiple Autoimmunity and Immunodeficiency Clinic; GI, gastrointestinal; CNS, central nervous system; DM, diabetes mellitus; SLE, systemic lupus erythematosus; LAD, lymphadenopathy; HSM, hepatosplenomegaly; AIE, autoimmune enteropathy; PLE, protein losing enteropathy; ANA, anti-nuclear antibodies; TPO, thyroid peroxidase antibodies; dsDNA, anti-double stranded DNA antibodies; ENA, extractable nuclear antigens; ANCA, anti-neutrophil cytoplasmic antibodies

Figure 3.. Infectious History of Patients in the MAID Clinic.

A) The percentage of patients in the MAID clinic with each type of infection is depicted in the graph. B) Seventy-three patients had recurrent sinopulmonary infections (self-reported by the patient), and the total number of patients with each type of sinopulmonary infections is depicted. C) Twenty-four patients had recurrent mucocutaneous infections (self-reported by the patient), and the type of pathogen that caused these infections is depicted. MAID, Multiple Autoimmunity and Immunodeficiency Clinic; GI, gastrointestinal; GU, genitourinary; CNS, central nervous system; RSV, respiratory syncytial virus

Figure 4.. Immunomodulatory Medications at Initial MAID Clinic Evaluation.

The number of patients taking a given medication at the first MAID clinic visit is shown in the graph. Patients may be on more than one immunomodulatory medication simultaneously. MAID, Multiple Autoimmunity and Immunodeficiency Clinic; IVIG, intravenous immunoglobulin; SQIg, subcutaneous immunoglobulin; Aza, azathioprine; TNF, tumor necrosis factor; MMF, mycophenolate mofetil; HCQ, hydroxychloroquine; 6MP, 6-mercaptopurine; MTX, methotrexate; LEF, leflunomide; CsA, cyclosporine; ABT, abatacept

Figure 5.. Immune Evaluation of Patients in MAID Clinic.

A) The percentage of patients in the MAID clinic with given immune system abnormality is depicted. Patients with low absolute numbers of B, T, and NK cells are included (124 of the 144 patients in the MAID cohort were screened for T/B/NK subsets). Patients with a low percentage of unswitched and/or switched B cells are included (97/144 patients screened). Patients with elevated CD4 and/or CD8 T cells are included (85/144 patients screened). B) The percentage of patients with the given low immunoglobulin is depicted (133/144 patients screened). C) The percentage of patients with the given immune system abnormality is depicted (42 patients were screened for DN T cells, 78 for IgE, 37 for γΔ T cells, 67 for CD21^lo B cells, and 51 for Treg cells). Normal values for all immune system parameters were determined based on age. MAID, Multiple Autoimmunity and Immunodeficiency Clinic; DN double negative; Treg, regulatory T cells

Figure 6.. Treatments Started in the MAID Clinic.

A) The number of patients in the MAID clinic who were started on the given treatment is depicted. B) Of the 16 patients started on non-biologic DMARDs, the propotion of patients started on each medication is depicted. C) Of the 7 patients started on biologic DMARDS, the proportion of patients started on each medication is depicted. DMARDs; disease-modifying antirheumatic drug; IVIG, intravenous immunoglobulin; bio, biologic; TNF, tumor necrosis factor