Neslihan E. Karaca, Turkey

Ege University Pediatric Allergy and Clinical Immunology

Presenter of 2 Presentations

Poster Display Innate Immunity

INTERLEUKIN-12/INTERFERON-GAMMA PATHWAY DISORDERS AND PREDISPOSITION TO ATYPICAL MYCOBACTERIAL INFECTIONS

Lecture Time
10:07 - 10:08
Room
Poster Area
Date
19.09.2019, Thursday
Session Time
10:00 - 17:00
Board Number
137
Presentation Topic
Innate Immunity

Abstract

Background and Aims

Mendelian susceptibility to mycobacterial disease (MSMD) due to inborn errors of IFN-γ immunity.is a rare primary immunodeficiency, triggered by non-tuberculous mycobacteria or Bacillus Calmette-Guérin (BCG) vaccines.

Methods

Nine patients (7 males, 2 females) diagnosed as Interleukin-12/Interferon-gamma pathway defects were included in the study.

Results

The diagnosis were IFN-γR1 complete defect (n = 1), IFN-γR2 partial defect (n=3) and IL-12Rβ1 defect (n=5). The rate of consanguineous marriage was 78% and the primary immunodeficiency family history was 56%. BCG vaccine was applied to all cases. The presentation symptoms were recurrent respiratory infections (100%), lymphadenitis (78%), chronic diarrhea (44%) and rash (11%). On physical examination, pathological findings were pulmonary involvement (44%), lymphadenitis (78%), hepatosplenomegaly (78%), generalized lymphoproliferation (44%), eczema (11%) and edema (11%). Laboratory tests showed leukocytosis, hypergammaglobulinemia and elevated erythrocyte sedimentation rate. M. Bovis, M. Avium intracellulare, M. Fortuitum and Salmonella were isolated from lymph nodes, bone marrow and liver. Leukocytoclastic vasculitis was observed in 2 cases and granulomatous dermatitis in 1 case. Splenectomy was performed in two patients because of hypersplenism. One case with IFN-γR1 complete defect died after hematopoietic stem cell transplantation and 1 patient with IL12-Rβ1 defect died due to sepsis at the age of 17 years. Four patients underwent regular recombinant IFN-γ treatment. One patient who had symptoms of Hyper IgE syndrome on admission found to have IL12-Rβ1 defect and benefited from regular IVIG therapy.

Conclusions

IL12/IFN-γ/IL23 defects should be considered in patients with BCG complications and non-tuberculous mycobacterial infection.Early hematopoietic stem cell transplantation should be performed in IFN-γR complete defects before the development of complications.

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Poster Display Other

TRNT1 DISEASE PRESENTING WITH CONGENITAL HEMOLYTIC ANEMIA AND HYPOGAMMAGLOBULINEMIA

Lecture Time
10:26 - 10:27
Room
Poster Area
Date
20.09.2019, Friday
Session Time
10:00 - 17:00
Board Number
130
Presentation Topic
Other

Abstract

Background and Aims

Although sideroblastic anemias may be associated with different etiologies, general abnormality is deterioration of mitochondrial heme biosynthesis in bone marrow erythroid cells. Biallelic mutations in the TRNT1(CCA-adding transfer-RNA nucleotidyl-transferase) gene have been shown to cause a syndromic form congenital sideroblastic anemia associated with B-cell lymphopenia, hypogammaglobulinemia, growth retardation and periodic fever syndrome(SIFD).

Methods

A 7-year-old boy presented with complaints of frequent upper respiratory tract infections and bronchitis since 6-months of age.He was the second-child of consanguineous healthy parents and followed-up by Hematology Department because of anemia for 4-years.Iron deficiency,hemoglobinopathies and immune hemolytic anemias were excluded.

Results

Physical examination findings on admission were as follows; weight and height percentiles were 10%,the liver was enlarged to 4cm and the spleen to 2cm palpabl below the costal margins. Laboratory investigations showed anemia (WBC 5590/mm3,Hb 8.2g/dl, Htc 24%,MCV 57fl,platelet 306000/mm3), anisocytosis,poikilositoz and ring sideroblasts in peripheral smear, hypogammaglobulinemia (IgG464mg/dl, IgM29mg/dl, IgA20mg/dl), negative Direct-coombs-test, normal lymhocyte subsets (CD3+67%,CD19+6%,CD3+CD4+28%,CD3+CD8+35%,CD3-CD16/56+14%) and inadequate specific-vaccine responses. Thorax CT showed nonspecific pulmonary nodules.The patient was followed-up with the preliminary diagnosis of common variable immunodeficiency and received regular intravenous-immunoglobulin replacement.A mild increase in immunoglobulin levels was observed with age.Targeted next-generation sequencing of a comprehensive IonAmpliSeq™PrimaryImmuneDeficiencyResearch Panel detected a homozygous mutation(c.914A>T,p.Asp305Val) in TRNT1 gene at the age of 14-years.

Conclusions

SIFD is due to loss-of-function mutations in the TRNT1 gene. Childhood TRNT1 disease/SIFD(OMIM#612907) is included in the antibody deficiencies group in IUIS Primary Immunodeficiency-2017 classification. The patient was presented to emphasize that TRNT1 disease should be considered in the differential diagnosis of anemia and hypogammaglobulinemia.

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