Clinical Features,genetic And Immunological Analysis Of Patients With LRBA And CTLA-4 Deficiency

PART ? CLINICAL FEATURES,GENETIC AND IMMUNOLOGICAL ANALYSIS OF PATIENTS WITH LRBA DEFICIENCYObjective: LPS-responsive beige-like anchor protein(LRBA)deficiency is a primary immunodeficiency associated with autoimmune manifestations and recurrent infections.In China,detailed clinical,genetic,and immunologic characteristics of LRBA-deficient patients were not described before.Methods: Five affected individuals from four non-consanguineous families were assessed by various clinical manifestations and immunological phenotypes,focusing on the B phenotypes.Result: Five indexed patients harbored compound heterozygous mutations in LRBA.With the exception of one mutation reported before,none had been identified previously.The most common clinical manifestations were autoimmunity and infection;none of the patients had chronic diarrhea,which is commonly reported in other studies.In addition to clear defects in Treg and Tfh cells were observed in four patients,abnormal B cell phenotypes were identified,including a reduced percentage of antibody-secreting B cells and an increased frequency of autoreactive B cells.Conclusion: We report five Chinese cases of LRBA deficiency caused by novel mutations in LRBA.The observed Treg cell deficiency and abnormities in B cell phenotypes might be an important indicator for autoimmune complications and hypogammaglobulinemia in LRBA deficiency.PART ? CLINICAL FEATURES AND IMMUNOLOGICAL ANALYSIS OF ONE FAMILY WITH CTLA-4 DEFICIENCYObjective: To investigate the clinical and immunological laboratory features,and CTLA-4 expression in one family with CTLA-4 deficiency.Methods: One patient and his maternal relatives were enrolled in this study.The clinical manifestation was analyzed and immunological laboratory features were assessed.Result: The patient was presented with chronic diarrhea,hypokalemia,hypogammaglobulinemia and lymphoid hyperplasia.Gene sequencing showed heterozygous mutation in CTLA-4.His mother and maternal grandfather were carrier.The numbers of Treg and CTLA-4 expression were reduced.The numbers of total B lymphocyte especially memory B cell were declined in patient and mother.Reduced percentage of antibody-secreting B cells and an increased frequency of autoreactive CD21 low B cell were observed.Clear increase in Tfh cells was indentified.TCRv? showed mild skewed,but their T lymphocyte proliferative response was normal.Receiving prednisone and mycophenolate therapy,the patient had ameliorative clinical outcome.Conclusion: One patient characteristic by autoimmunity and hypogammaglobulinemia was diagnosed with CTLA-4 deficiency.The observed Treg and B cell deficiency might be reminders for diagnose and treatment.PART ? NOVEL SPLICING MUTATION IN COMPLEMENT FACTOR I IN A CHINESE PATIENT WITH RECURRENT COMPLICATED MENINGO-ENCEPHALITISObjective: Complement deficiency is a rare kind of primary immunodeficiency diseases.This study was performed to investigate the clinical characteristics,genetic variation of Complement factor I(CFI)gene and the immunological features in a 6-year old male CFI-deficient patient with recurrent complicated meningo-encephalitis.Methods: C3 level,antibody levels,absolute and relative numbers of peripheral lymphocyte subsets were detected,while immune-associated gene mutations were evaluated by gene sequencing technology.Result: Data showed observable reduce of C3 level and a homozygous G>A substitution located in exon 5 splicing site(772+1)resulting in potentially false m RNA,which resulted in very low expression of CFI protein compared with age-matched healthy boys detected by ELISA.Parents of the patient were identified as heterozygous carriers of the same mutation.Conclusion: A novel splicing mutation of CFI gene has identified in a Chinese CFI-deficient patient with decreased expression of CFI protein.Patient with recurrent complicated meningo-encephalitis and decreased C3 level should be suspected as complement deficiency,thus C3 and CFI gene analysis should be performed for final diagnosis.