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العنوان
Immunological Profile of Patients with Skeletal Dysplasia and Disproportionate Short Stature /
المؤلف
Ghorab, Raghda Mohammed Mohammed Mostafa.
هيئة الاعداد
باحث / رغدة محمد محمد مصطفى غراب
مشرف / نهلة محمد زكريا يوسف
مشرف / شمس محمد خلوصي
مشرف / رشا محمد ممدوح عبده
مشرف / سامية علي التمتامي
مشرف / دعاء محمد عبد العزيز
تاريخ النشر
2018.
عدد الصفحات
198 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
أمراض الدم
تاريخ الإجازة
1/1/2018
مكان الإجازة
جامعة عين شمس - كلية الطب - الباثولوجيا الإكلينيكية
الفهرس
Only 14 pages are availabe for public view

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from 198

Abstract

Skeletal dysplasia point toward a group of disorders generally affecting bone and cartilage resulting in abnormalities in the development of the axial or the appendicular skeleton. This often results in disproportionate short stature (disproportionate dwarfism) which manifest as short-limbed dwarfism or short-trunk dwarfism.
Some of these disorders are occasionally associated with primary defects in the immune system where the immunodeficiency is labelled as “Syndromic Immunodeficiency”. Syndromic Immunodeficiency characterizes the association of primary immune defects with phenotypic abnormalities or laboratory findings implicating any other system involvement.
It is crucial to differentiate the primary defects from the secondary defects that arise from anatomical and physiological abnormalities due to the original malformation present. This would typically lead to providing the patient with optimal clinical care he/she needs by implementing appropriate and early treatment. Furthermore, it would guide along with the phenotypic abnormalities present in the patient to give proper genetic counselling regarding precise prognosis and possibilities of recurrence in other family members and future pregnancies depending on the expected pattern of inheritance.
The aim of this study was to establish a laboratory screening profile for the immune defects in cases of skeletal dysplasias with disproportionate short stature. We also aimed to define the immunologic phenotype of the studied skeletal dysplasias in order to identify the presence or absence of immune defects in cases of skeletal dysplasias with disproportionate short stature.
The current study included twenty-five patients with disproportionate dwarfism due to skeletal dysplasia. In addition, twenty healthy subjects, matched for age and gender, were included as a control group. Both patients and controls were categorized into two age groups: from 0-3 years and from more than 3- 15 years. The study was conducted in the period from November 2015 to August 2017 on patients visiting outpatient clinics of the Clinical Genetics Department mainly the Limb Malformations and Skeletal Dysplasia clinic at the NRC. Control samples were taken from those enrolled in projects undertaken at the Immunogenetics Department of the NRC. The laboratory work was done at the immunogenetics research lab of the NRC.
All patients under study were subjected to thorough clinical and radiographic evaluation along with the following laboratory investigations: CBC, investigations for assessment of the affected system, lymphocyte subset quantitation by flowcytometry, Igs quantitation by nephelometry and TRECs quantitation by real time PCR.
Results of the study revealed the presence of 9 cases of syndromic immunodeficiency in the studied patients; 5 in the younger age group (from 0-3 years) and 4 in the older age group (from >3-15 years) with a prevalence rate that equals 36% among the studied population. Four patients had findings indicative of humoral immunodeficiency and 5 showed a picture suggestive of combined immunodeficiency. Among the patients who were diagnosed with humoral immunodeficiency, 2 received immunotherapy (IVIG) with dramatic improvement in their clinical immune manifestation either through completely aborting incidence of infectious episodes or by significantly reducing the frequency and severity of them.
Age adjusted reference ranges of the measured immune parameters among control groups in this study were compatible with those established in other studies which investigated those parameters.
Comparative statistics that were done between patients with syndromic immunodeficiency and controls in the younger age group (from 0-3 years) regarding different immunological parameters studied showed statistically significant difference in the following parameters: CD16%, absolute CD16 which were higher in patients and CD19% and IgM which were lower among patients. In the older age group (from >3-15 years), only CD8% was statistically significant lower in patients when compared to controls.
Comparison between measured parameters among controls in the two age groups showed significant difference in the following parameters: CD19% and absolute CD19; being significantly higher in the younger age group, while CD8%, IgG and IgA were significantly higher in the older age group. The following parameters showed higher median values, although not statistically significant, in the younger age group: absolute lymphocyte count, CD3%, absolute CD3, CD4%, absolute CD4, TRECs/µl DNA, TRECs/ml WB and Log TRECs/ml WB. Contrarily, values of CD16%, absolute CD16 and IgM were higher, although statistically insignificant, in the older age group.
The following parameters showed statistically significant negative correlation with age of patients: absolute lymphocyte count, absolute CD3, CD19%, absolute CD19, absolute CD4, TRECs/µl DNA, TRECs/ml WB and log TRECs/ml WB, while the parameters which showed positive significant correlation were: CD16%, IgG and IgA.
Multiple regression analysis between different TRECs units used in our work and expected predictors suggests that expressing TRECs values per ml whole blood is the unit that is most consistent with the other laboratory parameters measured previously known to be acceptable predictors.
The correlation between the presence of immune manifestations during initial clinical evaluation and the presence of immune defects after laboratory workup in positive cases was significant. However, some patients showed evidence of immune defects after laboratory workup despite absence of clinical manifestations mentioned in the ten warning signs.