Background and Aims

Severe combined immunodeficiency with the presence of B lymphocytes (Nezelof syndrome) is manifested by a pronounced defect of cellular immunity with lymphopenia and thymic dysplasia. This condition is defined as a lymphocytic, normo-plasmocytic and normo-globulinemic aplasia.

Aim: evaluation of morphopathological changes in Nezelof syndrome

Methods

were evaluated data (medical records, morphopathological data, immunohistochemical staining) of 36 patients aged 0-18 years diagnosed at the Institute of Mother and Child from Moldova with primary immunodeficiency postmortem to detect any Nezelof syndrome.

Results

Nezelof syndrome was detected in 4 patients (11.1%). It is characterized by thymic hypoplasia and dysplastic changes defined by the presence of concentrically arranged epithelial cells and the total lack of Hassall corpuscles and its predecessors. There was also no corticomedullary segregation. Thymic parenchyma was composed only of a reticular stroma with total lymphocyte depletion (fig.1). Also, in the spleen and the lymph nodes, besides lymphocyte depletion, there were numerous plasmocites. The same changes were observed in the intestinal lymphoid follicles, especially the presence of plasmocites.

Conclusions

Thymic hypoplasia and dysplastic changes, manifested by the presence of pseudoglandular structures of the reticulo-epithelium, lack of Hassall corpuscles, and depletion of lymphocyte from the lymphoid tissue are morpfopatological data about Nezelof syndrome.

Background and Aims

Wiskott-Aldrich syndrome (WAS) is a rare, recurrent X-linked pathology, characterized by the triad: thrombocytopenia, eczema and recurrent immunodeficiency. WAS usually manifests in infancy, in most cases the first clinical features are hemorrhagic manifestations.

Aim: To describe two boys and 1 girl with WAS genetically confirmed with absolutely different onset of symptoms.

Methods

We reviewed medical records and blood counts, phenotyped peripheral blood lymphocytes.

Results

We describe 2 boys (P1 and P2) and 1 girl (P3) with early-onset of symptoms and mild cellular abnormalities. P1 from the age of one month has frequent severe respiratory infections (bronchiolitis, pneumonia, pneumonia with P. jirovecii) and from 4 months he also has eczema. P2 from the age of 1.5 months has high tendency to bleeding with haemorrhagic colitis, ecchymosis and petechiae, from the age of 3 months he is frequently hospitalized for respiratory infections, predominantly pneumonia. P3 at 3 months is hospitalized for pneumonia and haemorrhagic rash, after that monthly mother addresses with diffuse haemorrhagic rashes on the child skin. All patients have severe thrombocytopenia with normal MPV.

Conclusions

Despite an uncommon onset and a normal MPV, the association of severe thrombocytopenia with infections requires WAS suspicion and diagnosis.

Background and Aims

Primary immunodeficiency are genetically determined diseases characterized by lack of the function/a component of the immune system. Malignancies are one of the causes of death in PID. It has been demonstrated by epidemiological studies that cancer risk is 1.6-2.3 times higher in primary immunodeficiency than in the general population. The most common types of malignancies in PID are hematological malignancies, especially lymphomas.

Aim: evaluation of cases of hemoblastosis in patients diagnosed with primary immunodeficiency in the Republic of Moldova

Methods

were evaluated 51 patients (36 patients – post-mortem) aged 0-18 years diagnosed with primary immunodeficiency at the Mother and Child Institute of the Republic of Moldova. For the diagnosis of hematological malignancies were used: bone marrow biopsy, biopsy and lymph node histology, immunohistochemistry.

Results

Of the total number of cases, 3 (5.8%) children were identified with malignant neoplasms; with a boys : girls ratio=2:1. The mean age of diagnosis of malignancy was 9.5±8,6 years. In a child with Louis Bar syndrome and marked cervical lymphadenopathy, at the thoracic CT with multiple paraaortal and peribronchial ganglia, after thelymph node biopsy and histology, the diagnosis of non-Hodgkin's lymphoma, lymphoblastic form was etablished. For the other two children, non-Hodgkin's lymphoma, lymphoblastic form (in the patient with CVID) and acute lymphoblastic leukemia (in the Louis Bar patient) were identified in the morphopathological evaluation.

Conclusions

Patients with primary immunodeficiency have a high risk of developing cancer. Hematological malignancies is one of the most common types of malignancy in these patients.

Background and Aims

Primary immunodeficiencies are rare genetic diseases of the immune system. The manifestations of primary immunodeficiencies are extremely varied, often hidden under different masks. Despite the creation of alarm signs and improvement of diagnosis there are situations of delaying the diagnosis of primary immunodeficiency.

Aim: to determine the structure of primary immunodeficiencies among the pediatric population in Moldova

Methods

Over 25 years at the Institute of Mother and Child were evaluated 51 children with primary immunodeficiency 0-18 years of age by (general blood analysis, serum immunoglobulin determination, lymphocyte immunophenotyping, morphology and immunohistochemistry, molecular genetic methods)

Results

36 patients (70%) were diagnosed postmortem by degrading the specific features of the immune system organs and other organs. Of these 7 patients had DiGeorge syndrome with agenesis or hypoplasia of the thymus; 4 - Louis Bar syndrome, 4 - SCID type Nezelof, 6 - Swiss type SCID and 15 (41.6%) were diagnosed with non-classifiable primary immunodeficiency. Based on the evaluation of the alarm signs, the diagnosis was suspected and confirmed in 15 patients (30%): 3 – Bruton, 1 patient with SCID, 1 - CVID, 1 - hyper IgM and 9 patients with well-defined syndromes (3 - Louis Bar, 3 - WAS, 1 - Bloom, 1 - DiGeorge).

Conclusions

Morphopathological evaluation is important for diagnosis of PID. But the focus should be put on multidisciplinary collaboration to increase the early diagnosis rate of children with immunodeficiency.

Background and Aims

Bruton agammaglobulinemia is a hereditary (X-linked) immunodeficiency disorder characterized by the absence of mature B-cells, which leads to severe antibody deficiency and recurrent infections. Clinical manifestations occur as soon as the protective effect of maternal immunoglobulins decreases, approximately at the age of six months. The first sign is frequent respiratory infections, which can have serious progression.

Aim: evaluating the spectrum of infections in Bruton agammaglobulinemia

Methods

Were reviewed medical records of 4 patients with Bruton agammaglobulinemia focusing on immunoglobulins, phenotyped peripheral blood lymphocytes and infections.

Results

In all children the first sign of alarm was the frequent early-onset infections. In 2 of the children were present purulent infections with different localizations (meningitis, empyema, sinusitis, osteomyelitis) with progressive severe progression. Recurrent respiratory infections over time have complicated with chronic bronchopulmonary phenomena with bronchial deformities, pulmonary fibrosis, bronchiectasis. The immunological investigation in all patients indicated a reduction of serum immunoglobulin values: IgA - 1.78±0.9 mg/dl; IgM - 1.8±0.67 mg/dl; IgG - 6.75±0.54 mg/dl. Determination of lymphocyte populations in these patients resulted with normal T – 49±13.8% lymphocyte variation and a significant reduction in B cells of 8.8±3.03%.

Conclusions

Lack of antibodies to agammaglobulinemia Bruton leads to a polymorphism of infections with different localization, the respiratory system being predominantly affected.