Clinical Features And Immunological Analysis In 132 Patients With Wiskott-aldrich Syndrome And Two Families With X-linked Lymphoproliferative Disease

PART ?CLINICAL FEATURES AND GENOTYPE ANALYSIS IN 132 PATIENTS WITH WISKOTT-ALDRICH SYNDROMEObjective: To investigate the clinical and immunological laboratory features,gene mutations,treatment and prognosis in children with Wiskott-Aldrich syndrome(WAS).Method: The clinical,laboratory characteristics,treatment and prognosis of 132 children with WAS,who visited Children's Hospital of Chongqing Medical University from April 2000 to June 2015,were analyzed retrospectively.Result: All patients were males.The median age of disease onset was 15 days and the median age at diagnosis was 10 months.There were 112 cases with Classic WAS and 20 cases with X-linked thrombocytopenia(XLT).The median platelet value is 23×109/L(1×109/L ~ 80×109/L).All cases had the clinical characteristics of WAS including bleeding,eczema,recurrent respiratory infections.The initial symptoms including hemorrhage(75.0%),eczema(16.7%).21 cases with autoimmune diseases,one patient with leukemia.WAS protein(WASp)expression in 115 cases were measured by flow cytometry,of which,88 cases were negative,12 cases decreased,5 cases were normal,10 cases had double peak.81 kinds of mutation were found in 125 families,including 29 kinds of novel mutations.The proportion of CD3+ T cells(31.3%),CD3+CD4+ T cells(37.3%),CD3+CD8+ T cells(38.6%)declined in the periphery.The serum levels of IgG(51.1%),IgA(43.3%)and IgE(40.0%)increased,IgM(25.6%)reduced.In a total of 132 cases,72 cases remain survived,in which,36 cases received hematopoietic stem cell transplantation(HSCT),14 classic WAS patients received intravenous immunoglobulin therapy(IVIG).With regular IVIG therapy,the frequency of infections reduced and their symptoms were improved.Conclusion: The clinical characteristics of Wiskott-Aldrich syndrome were early age of onset,microthrombocytopenia,eczema and recurrent infections.The proportion of T cells could declinced,the serum levels of IgA,IgE increased and IgM reduced in patial patients.The WAS gene mutation and WASp detection were the key diagnostic methods.PART ?CLINICAL FEATURES AND IMMUNOLOGICAL ANALYSIS IN TWO FAMILIES WITH X-LINKED LYMPHOPROLIFERATIVE DISEASE TYPE-1Objective: To investigate the clinical and immunological laboratory features,mutations in SH2D1 A and SAP protein expression in four children of two families with X-linked lymphoproliferative disease type-1(XLP-1).Method: Four patients(Famliy A including Patient 1 and Patient 2,Famliy B including Patient 3 and Patient 4)and their maternal relatives were enrolled in this study.The clinical manifestation,EBV infection and chest CT scan were analyzed.The absolute and relative numbers of lymphocyte subsets,T lymphocyte proliferative response,SAP protein expression were assessed by flow cytometry.Quantification of signal joint TCR rearrangementexcision circle(sj TRECs),CDR3 spectratyping of TCRV? and gene mutation of SH2D1 A were detected by PCR based on genomic DNA or c DNA.Result: Four male patients from two families were diagnosed with XLP-1.The ages of disease onset were more than 1 year old,more than 1 year old,more than 1 month old and 6 months old.The ages at diagnosis were nine years and ten months old,sixteen years and eight months old,fourteen years and ten months old,four years and nine months old.All patients had recurrent infections and EBV infection.Patient 1,2,3 had agammaglobulinemia and Patient 4 had hypogammaglobulinemia.Chest CT scan showed all patients had atelectasis and pneumonia,and Patient 3 had bronchiectasis.Patient 3 was diagnosised as Burkitt lymphoma.For immunological function,all patients exhibited reduced CD4/CD8 ratios,increased numbers of terminally T lymphocyte,decreased number of NK cell.The numbers of total B lymphocyte and na?ve B lymphocyte were normal,but the number of memory B lymphocyte declined in all cases.Four patients' copy numbers of sj TRECs were low and CDR3 spectratypings of TCRv? showed mild skewed.But their T lymphocyte proliferative response was normal.SAP protein expression in four cases were measured by flow cytometry.Two patients from Family A were absent and two patients from Family B were decreased.SH2D1 A gene sequence analysis showed that the patients of Family A harbored a nonsense mutation(c.163 C>T;p.R55X)in exon 2.Their mother and two sisters were carriers.A missense mutation of SH2D1 A gene(c.278 G>A;p.G93D)in exon 3 was found in the patients of Family B.The mother was carrier.Four patients remain survived,Patient 3 gave up treatment,other three patients received IVIG therapy.Conclusion: Four patients with XLP-1 from two families characteried by agammaglobulinemia have an extreme vulnerability to EBV infection.The functions of T cell,B cell and NK cell are impaired at different stages.The detection of SAP protein and SH2D1 A gene were are the key methods for diagnosis of XLP-1.