Clinical and Immunological Characterization of Patients with Selective IgA Deficiency (SIgAD) in Colombia.
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1
Universidad de Antioquia, Grupo de Inmunodeficiencias Primarias, Colombia
Selective Immunoglobulin A Deficiency (SIgAD) is a Primary Immunodeficiency (PID) characterized by undetectable serum IgA (<7 mg/dl) with normal IgG and IgM and normal IgG antibody (Ab) responses to carbohydrate antigens in patients > 4 years old, who exhibit increased susceptibility to recurrent respiratory and gastrointestinal (GI) tract infections and autoimmune manifestations (http://esid.org/Working-Parties/Registry/Diagnosis-criteria). Previously, it has been shown in different cohorts that patients diagnosed with SIgAD might exhibit heterogeneous clinical and immune abnormalities that range from recurrent infections of the respiratory tract to autoimmune disorders (Bezrodnik, et al. Arch.argent.pediatr 2003). However, these abnormalities vary widely within those cohorts and there is not a consensus about the relevance of these findings and furthermore, the genetic basis of this PID are currently unknown. Therefore, we investigated if these clinical and immunological abnormalities are present in patients affected with SIgAD.
Data were collected from clinical and laboratory records of 7 patients admitted until April of 2014, who met current ESID criteria for SIgAD. Ig and Abs against T-cell dependent antigens were measured in serum. Flow cytometry was used to phenotype peripheral blood lymphocytes (PBL) subsets and T (PHA, anti-CD3 plus anti-CD28) and B cell proliferation (anti-IgM, CpG, SAC and rhIL-21 plus anti-CD40L).
Seven patients (5 females/2 males) born from apparently non-consanguineous parents were included and average age of onset of symptoms and of diagnosis was 6 (0.6 –18) and 10 (2.5 – 52) years old, respectively. All patients had normal serum levels of IgG and IgM with undetectable IgA (<7mg/dl) in at least two measurements (not less than 6 months) as well normal anti-tetanus and anti-diphtheria IgG Abs. We observed a wide spectrum of clinical findings with at least 2 different manifestations that included recurrent respiratory tract infections (otitis media), allergies (rhinitis, asthma, dermatitis) as the most frequent, followed by GI infections in 22.2% (diarrhea and recurrent abdominal pain); no autoimmune manifestations were observed. Phenotyping of PBL revealed normal percentages and total numbers of CD19+ B cells, CD3+ T cells and CD3+/CD4+ and CD3+CD8+ T cells as well as CD16+CD56+CD3- NK cells. Percentages and total numbers of CD45+CCR7+ naïve, CD45RA-CCR7+ central memory and CD45RA-CCR7- effector memory T cells as well as IgD+CD27- naïve, IgD+CD27+ marginal zone-like (MZL) and IgD-CD27+ isotype switched B cells were also normal. In addition, T and B cell lymphoproliferation in response to the different stimuli used were normal in all patients. However, we observed that IgA+CD27+ and IgA+CD27- B cells were absent in all patients in comparison with healthy controls.
Our preliminary findings show that our SIgAD patients exhibit heterogeneous clinical abnormalities ranging from recurrent infections to allergies but no autoimmunity so far. In addition, we haven’t found abnormalities in PB T or B cells, except for the absence of IgA+ B cells, and although this could partly explain the lack of serum IgA, currently this is unknown. We are currently determining secretory IgA in saliva in our patients in order to investigate the extent of this deficiency in our patients. We expect to include more patients in this ongoing study to continue characterizing this cohort and to further delineate possible monogenic causes for SIgAD using next generation sequencing and bioinformatics tools.
Acknowledgements
Financial support: Instituto Colombiano para el Desarrollo de la Ciencia y la Tecnología- COLCIENCIAS. Grant # 111556934592 and Universidad de Antioquia.
Keywords:
Immunoglobulins,
IgA,
IgA Deficiency,
Primary Immunodeficiencies,
Lymphocytes
Conference:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología, Medellin, Colombia, 13 Oct - 16 Oct, 2015.
Presentation Type:
Poster Presentation
Topic:
Immunodeficiencies
Citation:
Rojas Restrepo
JL,
Franco-Gallego
WA,
Villada
FA,
Moncada-Vélez
M,
Orrego
JC and
Franco
JL
(2015). Clinical and Immunological Characterization of Patients with Selective IgA Deficiency (SIgAD) in Colombia..
Front. Immunol.
Conference Abstract:
IMMUNOCOLOMBIA2015 - 11th Congress of the Latin American Association of Immunology - 10o. Congreso de la Asociación Colombiana de Alergia, Asma e Inmunología.
doi: 10.3389/conf.fimmu.2015.05.00133
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Received:
29 May 2015;
Published Online:
14 Sep 2015.
*
Correspondence:
Dr. Jose L Franco, Universidad de Antioquia, Grupo de Inmunodeficiencias Primarias, Medellín, Antioquia, Colombia, jose.franco@udea.edu.co