Transplantation of stem cells of embryonic liver in a patient with severe combined immunodeficiency

A patient had severe combined immunodeficiency syndrome and X-chromosomal recessive heredity. Since the parents and siblings were not suitable as HLA-compatible bone marrow donors, stem cells from embryonic liver were transplanted intravenously in 3 stages (6 X 10(6); 3.5 X 10(6), and 9 X 10(7]. Transplantation was tolerated well; there were no signs of a graft-versus-host reaction. Examination of the immunological condition after transplantation showed evidence of T-cell reconstitution, immunohistochemistry revealed beginning immune globulin production. The child died at the age of 5 months due to respiratory failure.     

Bone marrow transplantation for severe combined immunodeficiency disease

Patients who received bone marrow transplantation (=BMT) for the treatment of severe combined immunodeficiency (=SCID), and who were reported in the medical literature from 1968 to 1977, were collected and analysed. Eighteen of these 80 children are still alive, 10 months to 9 years after transplantation. It is thus the first successful form of therapy for this otherwise invariably fatal disease.Fifteen of the 18 survivors received bone marrow cells from HLA and MLC compatible donors; the remaining 3 survivors received grafts from MLC-compatible but HLA-incompatible donors. Bone marrow transplantation is the treatment of choice for SCID when recipient and donor are HLA-and MLC-identical. All patients who received MLC-incompatible grafts died, and bone marrow transplantation for SCID from MLC-incompatible donors should be abandoned.Mild-to-severe graft-versus-host disease (=GVHD) occurred in spite of HLA- and/or MLC-compatibility, with some correlation to the number of cells transplanted. This should preferably be kept below 50 million cells per kilo body weight. Infection was the chief cause of death in all groups. Strict reverse isolation, bowel decontamination and routine pre-and post-transplant Pneumocystis carinii prophylactic treatment are recommended.The clinical picture and laboratory findings of these 80 children before BMT did not differ from non-transplanted SCID patients. Three of the 18 survivors are adenosinedeaminase deficient.     

Noma in children with severe combined immunodeficiency

Three Native American children with severe combined immunodeficiency developed noma, a necrotizing gingivostomatitis not previously reported in this country. The similarity between the clinical findings and those observed in monkeys with simian AIDS prompted us to evaluate our patients and their families for human retroviral infection. Antibodies to HTLV-I or HTLV-III/LAV proteins were not identified in patients nor in their family members. Standard bacterial and viral cultures similarly failed to identify a suspect pathogen.     

Nursing care of the premature infant with severe combined immunodeficiency disease

Diagnosis and treatment of severe combined immunodeficiency disease (SCID) is documented in fetuses, term infants, and older children; however, there is very little information on its diagnosis and treatment in premature infants. When Duke University Medical Center's first preterm infant with a known SCID history was delivered, in June 1999, there was no defined protocol for the infant's nursing care. Although many of the guidelines for nursing care of the premature infant population (< or = 36 weeks) apply, there are important considerations for preterm infants with an SCID diagnosis. This article provides background on SCID and identifies those special considerations--namely, multidisciplinary communication, infection prevention, thorough physical assessments, and parental support.     

Chimerism in a child with severe combined immunodeficiency: a case report

Severe combined immunodeficiency (SCID) represents a group of rare, sometimes fatal, congenital disorders in which there is a combined absence of T-lymphocyte and B-lymphocyte function. Children with SCID die within two years of age, if untreated. The effective treatment for SCID is a hematopoietic stem cell transplantation (HSCT). It has been repeatedly described that in peripheral blood of infants with SCID maternal T cells can be found. Here we report a case of blood chimerism in a one-year-old boy with SCID.     

Review: Why screen for severe combined immunodeficiency disease?

Newborn screening for severe combined immunodeficiency (SCID) is now routinely performed in many countries across Europe and around the world. The number of T-cell receptor excision circles (TRECs) reflects T cell levels. TREC quantification is possible using dried blood spot (DBS) samples already collected from newborns to screen for other conditions. This method is very sensitive and highly specific. Data in the literature show that the survival rate for children with SCID is much higher when the disease is detected through early screening, as opposed to a later diagnosis. Newborns diagnosed with SCID may receive the appropriate care quickly, before the onset of serious infectious complications, which raises survival rates, improves quality of life, and limits side effects and treatment costs. At the request of the French Ministry of Health, France's National Authority for Health (Haute Autorité de Santé) is expected to issue recommendations on this topic soon. The nationwide DEPISTREC study, involving 48 maternity units across France, showed that routine SCID screening is feasible and effective. Such screening offers the additional benefit of also diagnosing non-SCID lymphopenia within the infant population.     

婴儿原发性严重联合免疫缺陷病并发结核性指骨炎1例

患儿,男,5个月,因发热、咳嗽1月余入院.患儿于1月余前出现咳嗽,伴发热,体温最高39℃,就诊于多家医院,先后给予阿莫西林/克拉维酸钾、头孢曲松钠、头孢呋辛钠、美罗培南、万古霉素、阿奇霉素等抗生素静脉滴注治疗及输注丙种球蛋白(IVIG),病情无好转.发病以来精神、食欲差,大便呈稀糊状,小便正常.否认结核病接触史.既往多次患鹅口疮.足月顺产,生后常规接种卡介苗,3个月后出现卡疤.否认遗传病家族史.     

Cerebral lymphoma in an adenosine deaminase-deficient patient with severe combined immunodeficiency receiving polyethylene glycol-conjugated adenosine deaminase

Polyethylene glycol-conjugated adenosine deaminase (PEG-ADA) provides an alternate therapy to mismatched stem cell transplantation for patients with ADA-deficient severe combined immunodeficiency. Although replacement therapy with PEG-ADA is effective in preventing infections, immune function does not return to normal, and most patients remain lymphopenic. Information is limited regarding the prognosis of patients on long-term ADA-replacement therapy. Here we present a case of a 10-year-old child who was diagnosed with ADA-severe combined immunodeficiency at 4 weeks of age after contracting pneumonia. Treatment with PEG-ADA was begun, the biochemical markers of ADA deficiency normalized, and his clinical progress was very good without significant infections. At 10 years of age, after presenting with headaches and cranial nerve deficits, he was diagnosed with Epstein-Barr virus-positive malignant brain lymphoma. It did not respond to various regimens of aggressive chemotherapy, and the patient expired 5 months later. We speculate that in this patient the immunologic surveillance by T cells may have been defective with respect to elimination of Epstein-Barr virus-infected cells, hence the formation of neoplasm. The possible mechanisms underlying such pathology are reviewed.     

不典型严重联合免疫缺陷病 7 例诊治分析

目的探讨不典型严重联合免疫缺陷病(SCID)的诊断和治疗。方法回顾分析2012年9月-2017年6月证实为IL2RG、JAK3和RAG1突变的7例不典型SCID患儿的临床资料。结果 7例患儿中,婴儿5例,幼儿及学龄期儿童各1例;6例为男性、1例为女性。例2、4、6为经典SCID临床表型,例1、3、5、7为不典型SCID临床表型,例6临床诊断Omenn综合征。例2、5为经典SCID免疫表型,例1、3、4、6、7为不典型SCID免疫表型,例1有母体嵌合。二代测序提示,例1为复合杂合JAK3突变c.3097-1GA/c.946-950GCGGAACins GGT;例2、3、4为IL2RG突变,分别为c.865CT/p.R289X、c.664 CT/R 222 C、52 del G;例5为杂合JAK 3突变c.2150 AG/p.E 717 G、c.1915-2 AG。Sanger测序提示,例6为复合杂合的RAG1突变c.994CT/p.R332X、c.1439GA/p.S480N;例7为纯合的RAG1突变c.2095CT/p.R699W。结论 SCID基因突变在一定情况下可导致不典型的临床和/或免疫表现。     

Chemotactic defects in severe combined immunodeficiency.

Cellular and humoral components of leukotaxis were studied serially in four male infants with severe combined immunodeficiency disease. Two of the four, both lacking B and T cells initially, had a significant defect in neutrophil and monocyte chemotaxis. The other two, who had a high number of immunoglobulin-bearing cells (B cells), did not have these cellular abnormalities. It contrast, defective generation of chemotactic factor following endotoxin activation was observed in all patients. The defects were corrected coincident with or soon after successful engraftment of either bone marrow or fetal tissues. The reported deficiencies may be another manifestation of the heterogeneity in SCID.     

Chronic inflammatory bowel disease in a patient with common variable immunodeficiency

Common variable immunodeficiency (CVID) is a primary defect of the immune system involving an increased risk of respiratory and digestive tract infections and autoimmune diseases. Recently, it has been reported that chronic inflammatory bowel disease (CIBD) might occur with increased frequency (20%) in patients with CVID. A nine-year-old boy with CVID developed CIBD during follow-up and periodic intravenous immunoglobulin administration. Serum tumor necrosis factor-a concentration, which is suggested to show disease activity in CBD, was very high. The patient's radiological evaluation, both in active and remission periods, had characteristic features of CBD. We herewith present and discuss this case with both diseases, CVID and CIBD.