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CNAA / Theses / 2007 / May /

The morphogenesis of some congenital immunodeficiences

Author: Lilia Siniţîna
Degree:doctor of medicine
Speciality: 14.00.15 - Pathological Anatomy
Scientific adviser: Ion Fuior
doctor habilitat, professor, Public Medical Sanitary Intitution Scientific Research Institute of Mother and Child Health Care
Scientific council:


The thesis was presented on the 30 May, 2007
Approved by NCAA on the 20 September, 2007


Adobe PDF document0.46 Mb / in romanian


CZU 616-097-053.1+616-091

Adobe PDF document 9.84 Mb / in romanian
157 pages


Congenital immune deficiency, primary immunodeficiency syndrome, DiGeorge, Louis Bar, Nezelof, thymus dysplasia, reticulo-epithelium, accidental thymus transformation, intrauterine infection, apoptosis, autophagia, lymphocytes, lymphocytes depletion, cortical-medullar segregation, corpuscles Hassall, endothelial cells, viral inclusions, monoclonal antibodies, electronic microscopy


The thesis is dedicated to the particularities of congenital immune deficiencies of morphogenesis determined by the action of hereditary factors and intrauterine infection. Within the study, were assessed the incidence of primary congenital immune deficient syndromes, as well as the rate of most frequently identified syndromes. Thymus showed various dysplastic defective tissue architectural changes, which were attributed to different primary congenital immunodeficiency syndromes with well-defined morphology based on the morphological picture. Depending on the morphologic changes, there were identified the following congenital immunodeficiency syndromes: DiGeorge syndrome, Louis Bar syndrome, Nezelof syndrome and Swiss-type combined congenital immunodeficiency. The architectural transformation of the thymus tissue that displayed with severe dysplastic changes with constant morphological picture, yet could not define any specific hereditary determined immunodeficiencies, were included in the group of unclassifiable primary immunodeficiency syndromes, taking into account that tissue dysplasia is the basis of the primary immunodeficiency syndrome. Although, it was seen a significant variety of dysplasia, some common features were established within the unclassificable primary immunodeficiency syndrome, this way making possible a categorization of the given syndromes, depending on the affected tissular component. As a result, there were distinguished the following unclassifiable primary immunodeficiencies: stromal, cambial, differentiation immunodeficiency and thymomegaly. Stromal unclassifiable primary immunodeficiency syndromes include different defective dysplastic changes of the stromal reticulo-epithelium, the cambial ones - alteration of the cambial zone, differentiation immunodeficiency - dysplasia associated with architectural alterations of the organ and thymomegaly - lymphoid hyperplasia.

Children with primary congenital immunodeficiency, particularly DiGeorge syndrome, simultaneously with severe changes of the immune system, displayed in our study, several stigmas for dysembriogenesis, as well as diverse congenital malformations, the major share being held by different types of cardiovascular malformations, especially intraventricular septum and aorta arch defects.

Our study assessed that 89,2% of children usually died due to inflammatory diseases, following leucosis and malignant tumors. Even though the immune diseases mentioned above are extremely severe, frequently leading to death, in some cases the treatment is possible by application of thymus and bone marrow transplant. Considering the severity of these conditions, the birth of a child with primary immunodeficiency syndrome must be prevented, and implementation of the new technologies such as molecular diagnosis and genetic counseling, would largely contribute to prenatal and preconceptional diagnosis, and therefore making possible assessing the recurrence risks for subsequent pregnancies.

In the given context, the implementation of a Record for Primary Immunodeficiencies in Moldova similar to the registers of Immunological Deficiencies Foundation (USA), European Society for Primary Immunodeficiencies (ESID) and those recently established in Latin America (12 countries) and Iran, would be a first step in evaluating congenital primary immunodeficiency syndromes.

Another direction in the presented study was the assessment of intrauterine infection impact on the immune system, particularly thymus, spleen and lymphatic ganglia. As the result of the performed study, by applying complex investigation methods, including modern statistic analysis, it was concluded that the impact of intrauterine infections on the immune system of the fetus results in the evolution of secondary congenital imunodeficiencies, which display with high incidence of thymic transformation (97,4%); initially there occurs activation of immune reactions, while in the advanced stages of the process suppression signs dominate. The study showed that morphological reshaping in the immune organs mainly occur under the influence of viral-bacterial combinations, because pronounced evolution of the accidental thymus transformation was the main characteristic feature. Of equal value are viral intrauterine infections - main factor in the onset of immunodepressive process, following direct lymphocyte alterations, and additional bacterial infection. The immunological study of cellular components with monoclonal antibodies concerning children with intrauterine infection has established limphopenya, preponderant T cellular insufficiency, disbalanced between the imunoreglative subpopulations.

At the same time, the electron-optic examination showed that lymphocyte depletion in the thymus of the children born in mothers with intrauterine infection, within accidental thymus transformation, is induced mainly by the abusive apoptosis process, while the autophagia phenomenon, noticed in different thymus cellular populations, may lead not only to lymphocyte depression, but to early lipid dystrophy of the thymus cellular elements.

Thus, the morphogenesis of congenital immunodeficiency syndromes, as an ontogenetic expression of deficient function of immune system, is determined by the interrelation of hereditary factors and intrauterine infection.