Antibody deficiency and autoimmunity in 22q11.2 deletion syndrome

Background: Although severe T cell immunodeficiency in DiGeorge anomaly is rare, previous studies of humoral function in these patients have found no antibody abnormalities but have not examined the response to polysaccharide antigens. Isolated cases of autoimmunity have been reported. Several patients with 22q11.2 deletion attending our immunology clinic suffered recurrent sinopulmonary infection or autoimmune phenomena. Aims: To investigate humoral immunodeficiency, particularly pneumococcal polysaccharide antibody deficiency, and autoimmune phenomena in a cohort of patients with 22q11.2 deletion. Methods: A history of severe or recurrent infection and autoimmune symptoms were noted. Lymphocyte subsets, immunoglobulins, IgG subclasses, specific vaccine antibodies, and autoantibodies were measured. Subjects were vaccinated with appropriate antigens as indicated. Results: Of 32 patients identified, 26 (81%) had severe or recurrent infection, of which 13 (50%) had abnormal serum immunoglobulin measurements and 11/20 ≥4 years old (55%) had an abnormal response to pneumococcal polysaccharide. Ten of 30 patients (33%) had autoimmune phenomena; six (20%) were symptomatic. Conclusions: Humoral immunodeficiency is more common than previously recognised in patients with 22q11.2 deletion. Normal T cell function and immunoglobulin levels do not exclude poor specific antibody responses. Patients should be referred for formal immunological assessment of cellular and humoral immune function.     

Antibody deficiency and autoimmunity in 22q11.2 deletion syndrome.

BACKGROUND: Although severe T cell immunodeficiency in DiGeorge anomaly is rare, previous studies of humoral function in these patients have found no antibody abnormalities but have not examined the response to polysaccharide antigens. Isolated cases of autoimmunity have been reported. Several patients with 22q11.2 deletion attending our immunology clinic suffered recurrent sinopulmonary infection or autoimmune phenomena. AIMS: To investigate humoral immunodeficiency, particularly pneumococcal polysaccharide antibody deficiency, and autoimmune phenomena in a cohort of patients with 22q11.2 deletion. METHODS: A history of severe or recurrent infection and autoimmune symptoms were noted. Lymphocyte subsets, immunoglobulins, IgG subclasses, specific vaccine antibodies, and autoantibodies were measured. Subjects were vaccinated with appropriate antigens as indicated. RESULTS: Of 32 patients identified, 26 (81%) had severe or recurrent infection, of which 13 (50%) had abnormal serum immunoglobulin measurements and 11/20 >/=4 years old (55%) had an abnormal response to pneumococcal polysaccharide. Ten of 30 patients (33%) had autoimmune phenomena; six (20%) were symptomatic. CONCLUSIONS: Humoral immunodeficiency is more common than previously recognised in patients with 22q11.2 deletion. Normal T cell function and immunoglobulin levels do not exclude poor specific antibody responses. Patients should be referred for formal immunological assessment of cellular and humoral immune function.     

Prophylaxis of vitamin D deficiency in hypothyroidism in the newborn infant

This study deals with the relationship between the occurrence of hypercalcemia and the administration of prophylactic doses of vitamin D in children with hypothyroidism, before and during L-thyroxine (LT4) treatment. The goal of the study was to determine the dosage of vitamin D necessary to prevent rickets without inducing hypercalcemia. There was a 23% prevalence of hypercalcemia at the time of the diagnosis of hypothyroidism by screening whereas it was 21% in the children who were not given vitamin D during the first 3 months of LT4 treatment. This figure was significantly higher in those who were given vitamin D during the first 3 months of treatment and reached 70%. However, one of the 19 children not given vitamin D presented with biological signs evoking vitamin D deficiency. In conclusion, in hypothyroid infants, vitamin D should be administered carefully during the first 6 months of treatment and restricted to children at risk for developing vitamin D deficiency.     

慢性移植物抗宿主病的预防和治疗

目的　分析儿童异基因造血干细胞移植(allo-HSCT)后慢性移植物抗宿主病 (cGVHD)的特点及甲泼尼龙(MP)、吗替麦考酚酯(MMF)与他克莫司(FK506)或环孢素A(CSA)联合免疫抑制治疗的效果,探讨有效治疗方案。方法　共进行异基因造血干细胞移植 45例, 30例完全植入。完全植入的患儿中脐血移植(UCBT)17例,异基因外周血干细胞移植 (PBSCT) 13例。GVHD的预防采用CSA、MP、氨甲蝶呤及MMF等组合的方案。cGVHD患者采用MP+MMF+FK506或MMF+CSA联合治疗方案。结果　30例完全植入的患儿中发生cGVHD者 9例(30% );其中血缘相关PBSCT13例中发生cGVHD6例(46% );UCBT者完全植入 17例,发生cGVHD3例(18% )。急性GVHD迁延者 6例(67% )。1例患儿经CSA+MMF联合治疗痊愈; 8例采用MP+MMF+FK506“三联”治疗,cGVHD症状均得到有效控制,有效率为 100%, 2例分别并发巨细胞病毒间质性肺炎或败血症死亡,死亡率为22%; 7例无事件生存>3年(78% )。副作用有肝损害、肾损害、高血压、关节滑膜炎、心律失常,均在减药或停药、对症处理后毒副作用消失。感染是主要的合并症和死亡原因。结论　PBSCT者cGVHD发生率较UCBT者高;急性GVHD迁延是发生cGVHD的高危因素;选用包含MP、MMF、FK506 (或CSA)的 2~3种药物联合免疫治疗cGVHD,效果理想,患儿均能耐受,是     

Immunthrombocytopenic purpura as a model for pathogenesis and treatment of autoimmunity

In honour of Professor Rossi's 80th birthday we review the development of our understanding of the immune and auto-immune nature of the pathogenesis of immune thrombocytopenic purpura (ITP). The immune aspects have been documented by postviral alterations of the cellular and humoral immune system, by new methods of specific auto-antibody detection against platelet glycoproteins and by the therapeutic effect of administering immunoglobulin concentrate from healthy blood donors. The various possible mechanisms of action of immunoglobulin treatment have led to use of this treatment as an alternative for other immune-related disorders. The treatment of severe chronic ITP in children, however, remains unsatisfactory. With a new international clinical and laboratory study of children and adolescents with early chronic ITP we are continuing the investigation of the pathogenesis and treatment of ITP.     

Sensorineural hearing loss in primary antibody deficiency disorders

To evaluate the hearing function in patients affected by primary antibody deficiency disorders. Forty-seven patients, 25 of whom were affected by X-linked agammaglobulinemia and 22 of whom were affected by common variable immunodeficiency were evaluated with audiologic tests that included pure tone audiometry, acoustic immittance assessment and auditory brainstem-evoked response. Eighteen patients (38%), 7 with X-linked agammaglobulinemia and 11 with common variable immunodeficiency, showed sensorineural hearing loss, bilateral in 12 and unilateral in 6. Our data underline the high frequency of hearing loss in patients with antibody deficiency and suggest that a systematic audiologic evaluation should be part of the clinical care of these patients.     

Tuberculous meningitis and antibody deficiency disease (author's transl)]

A 13 year old girl not vaccinated with BCG became ill with tuberculous meningitis. After administration of 30 g of Streptomycin, cell counts and protein concentrations of the cerebro-spinal fluid returned to normal values. After continuation of antituberculous therapy without Streptomycin, the patient relapsed, and Streptomycin had to be given for 14 months. Defect in humoral immunity was diagnosed with low IgG and low titers of antiviral antibodies. For this reason the patient was additionally treated with passive administration of antibodies.