Clinical Characteristics Of Wiskott-aldich Syndrome With Autoimmune Diseases

Objective: To describe the clinical features of Wiskott-Aldrichsyndrome (WAS) with autoimmune diseases (AD) in the Children’sHospital of Chongqing Medical University, in order to prompt earlydiagnosis and proper treatment of autoimmune diseases occurring duringthe clinical course of WAS.Methods: The clinical data of53cases of WAS who visited ourhospital from April2004to January2014were analyzed retrospectively.All the patients were diagnosed by mutation analysis and flow cytometricdectection of WAS protein (WASp). The clinical characteristics, laboratoryfindings, treatment and prognosis of patients with AD were analyzed.According to presence of AD or not, the patients were divided into ADgroup or non-AD group. The immunological differences between the twogroups were compared.Results:1. Out of the53cases of WAS,14cases (26%) presented atleast one autoimmune complication. All the patients were male. Thepatients were diagnosed with WAS at a age of2to147months with median age of12months. The median age of occurrence of AD was17.5months. Autoimmune hemolytic anemia (AIHA) was the most commoncondition and was detected in12cases (23%). Other complicationsincluded immune thrombocytopenia (ITP, n=1), immune neutropenia(n=1), autoimmune arthritis (n=1), renal injury (n=1), each accounting for2%of the total WAS cases. Twelve patients had a single autoimmunecomplication, whereas two had two complications, one patient with AIHAand ITP, another with AIHA and immune neutropenia.2. Among the53cases,6of them were X-linked thrombocytopenia(XLT) with clinical scores of2, the others were classic WAS with clinicalscores of3to5except that one case was initially diagnosed as XLT with aclinical score of2and progressed into clinical score of5because ofpresence of AD. Autoimmune complications were seen in28%of thepatients with classic WAS, and14%of the patients with XLT.3. All the patients had a onset of AIHA before the age of4years.Themain manifestation in the AIHA children was anemia (100%), jaundice(25%), dark urine (17%). In all cases, the direct Coombs test was positive.Chronic swelling and multiple joint pains were the symptoms of immunearthritis that were observed. Renal injury showed recurrent microscopichematuria, renal biopsy was not done due to persistant thrombocytopenia.The onset age of arthritis and renal injury was after eight years.4. Serum IgG (8/11) and IgA (6/11) levels were increased in the majority of patients, while serum IgM (6/11) levels were decreased.Peripheral CD3+T cells were decreased in four cases (4/11), CD4+T cellswere decreased with an inverted ratio of CD4+/CD8+in six cases(6/11).Peripheral CD19+B cells (7/11) and CD56++CD16+NK cells (8/11)were normal in most cases. No significant difference was detected betweenthe AD group and the non-AD group (P＞0.05).5. Eight cases of AIHA underwent hematopoietic stem celltransplantation (HSCT), AIHA occurred before transplantation in3cases,and after transplantation in5cases. One-third of the AIHA patientsreceived steroids treatment and the other two-thirds patients receivedsteroids combined with intravenous immunoglobin (IVIG) and/orimmunosuppressive therapy. Among the patients treated,42%experiencedpartial remission (PR),33%experienced complete remission (CR),17%ofthe patients were non-responder to the treatment, and8%of the patientsrelapsed after initial responsiveness. Five patients (42%) died eventually, ofthese three died of pulmonary infection after transplantation, and the othertwo died of intracranial hemorrhage and pulmonary hemorrhage. IVIG waseffective in arthritis, while the renal injury patient developed chronic renalfunction failure and needed long-term steroids and immunosuppressivetherapy.Conclusion: Autoimmune complications in the course of WAS arerelatively frequent. The Chinese patients with WAS mainly presentd AIHA. Steroids, IVIG and immunesuppressor were partially effective or effectivein a short-term. Other autoimmune complications may also be seenoccasionally, such as thrombocytopenia, neutropenia and arthritis and renalinjury. AD is one of the major threats during the life span of WAS and XLT.HSCT with the matched donor appears to be the final solution for savingthe life of WAS patients and also curing the autoimmune complications.