Autoimmune and Inflammatory Manifestations in 247 Patients with Primary Immunodeficiency—a Report from the Slovenian National Registry

Abstract

An abnormal regulation of immune responses leads to autoimmune and inflammatory manifestations in patients with primary immunodeficiencies (PIDs). The objective of our study was to evaluate the frequency of non-infectious and non-malignant manifestations in a large cohort of patients included in the Slovenian national PID registry and to assess the time of manifestation onset with respect to the time of PID diagnosis. Medical records of registered patients were reviewed. Data on autoimmunity, lymphoproliferation, autoinflammation, allergies, PID diagnosis, and underlying genetic defects were collected and analyzed. The time of each manifestation onset was determined and compared with the time of PID diagnosis. As of May 2015, 247 patients with 50 different PIDs were registered in the Slovenian national PID registry (147 males, 100 females; mean age 20 years). Mean disease duration was 14 years; 78 % of patients were younger than 18 years; and 22 % of patients were adults. Diagnosis of PID was genetically confirmed in 51 % of patients. Non-infectious and non-malignant manifestations were present in 69/235 (29 %) patients, including autoimmune manifestations in 52/235 (22 %), lymphoproliferative/granulomatous in 28/235 (12 %), autoinflammatory in 12/247 (5 %), and allergic manifestations in 10/235 (4 %) of all registered patients. Autoimmune manifestations were present in all patients whose PIDs were classified as diseases of immune dysregulation, 47 % of patients with chronic granulomatous disease, and 38 % of patients with predominantly antibody immune deficiencies. A high prevalence of non-infectious and non-malignant manifestations among patients in the Slovenian national PID registry suggests common genetic factors of autoimmunity, inflammation, and immunodeficiency. Patients with PID should be routinely screened for autoimmune and inflammatory manifestations at the time of PID diagnosis and during the long-term follow up.

Peripheral Blood Lymphocyte Phenotype Differentiates Secondary Antibody Deficiency in Rheumatic Disease from Primary Antibody Deficiency

“…PID and especially CVID may manifest as autoimmune diseases [6][7][8][9], which necessitates anti-inflammatory treatment with drugs that can result in hypogammaglobulinemia, independently of an underlying PID [2]. Measurement of immunoglobulin levels before starting an anti-inflammatory treatment, likely to cause hypogammaglobulinemia is therefore extremely important, as it may identify a preexisting hypogammaglobulinemia.…”

“…Besides bacterial infections due to primary antibody failure, CVID may manifest with autoimmunity, granulomatous and/or lymphoproliferative disease [6]. Autoimmunity in CVID includes rheumatic disease, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) [7][8][9]. These conditions necessitate anti-inflammatory treatment, which could lead to hypogammaglobulinemia even in the absence of a PID.…”

“…In other words, the diagnosis of a PID is clear in case the diagnosis of hypogammaglobulinemia precedes immunosuppressive treatment of autoimmune or lymphoproliferative conditions. However, autoimmunity or lymphoproliferative disease and introduction of immunosuppressive treatment could precede the diagnosis of hypogammaglobulinemia [8][9][10][11][12]. The relatively recent discovery of monogenic disorders manifesting as CVID and subsequent studies of cohorts of patients with common monogenic defects revealed that hypogammaglobulinemia in primary immunodeficiency may have a later onset than autoimmunity or lymphoproliferative disease, which can phenotypically prevail [13][14][15][16].…”

The Italian Registry for Primary Immunodeficiencies (Italian Primary Immunodeficiency Network; IPINet): Twenty Years of Experience (1999–2019)

“…Organized registries represent an efficient and well-defined instrument for better characterization and understanding of rare diseases, with positive impact on the clinical management of affected patients and on the comprehension of the natural history of the disease [3,4]. In the last few decades, registries have been created for primary immunodeficiencies in several countries around the world in order to better define the distribution and features of patients affected with these disorders [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19].…”

Functional Complement Analysis Can Predict Genetic Testing Results and Long-Term Outcome in Patients With Complement Deficiencies

“…The Slovenian national PID registry was established in 2007 and compiles data of all patients with PID evaluated at the secondary and tertiary care hospitals in Slovenia since January 1977. The methodology of the registry was described elsewhere ( 7 ). See supplementary material for detailed description of methods.…”