Humans ; Severe Combined Immunodeficiency ; therapy

Humans ; Severe Combined Immunodeficiency/therapy*

Severe combined immunodeficiency disease (SCID) is a group of rare congenital diseases characterized by severe deficiencies in T lymphocyte counts and/or function. The recurrent, persistent and severe infections are its clinical manifestations. Neonatal screening and immune system reconstruction would improve the prognosis of SCID children. Newborn screening programs based on T-cell receptor excision circles (TRECs) quantitative detection have been carried out in clinical practice, however, the methods still have some limitations. Other new methods such as mass spectrometry and T lymphocyte-specific biomarker assays are still under investigation. Hematopoietic stem cell transplantation and gene therapy are the two main methods for reconstructing immune function in SCID children. Through improving the success rate of transplantation and the long-term safety and stability of viral vectors, some achievements have been made by many centers already. However, large-scale prospective studies are needed for evaluation of the long-term efficacy. In this article, the recent progress in newborn screening and immune reconstitution of SCID is reviewed.
Humans ; Immune Reconstitution ; Infant, Newborn ; Neonatal Screening ; trends ; Prospective Studies ; Severe Combined Immunodeficiency ; therapy ; T-Lymphocytes

In severe combined immunodeficiency disease, both T and B cell functions are diminished or absent and affected usually succumb to overwhelming infection within the first year of life. We are reporting a case with severe combined immunodeficiency, Swiss type who suffered from interstitial pneumonia which cleared by treatment with recombinant human interferon gamma. In this case, we don't know the exact mechanism which caused the clearing of the interstitial pneumonia. However, we can speculate that antiviral action and activated macrophages or monocytes, through the recombinant human interferon gamma, might exert its effect on interstitial pneumonia. Though we should extend its application to more cases of SCID with interstitial pneumonia, this report may suggests a new application for interferon-gamma as a potential corrective and therapeutic agent for interstitial pneumonia in congenital immunodeficiency diseases.
Case Report ; Human ; Infant ; Interferon-gamma, Recombinant/*therapeutic use ; Male ; Pulmonary Fibrosis/*therapy ; Severe Combined Immunodeficiency/*complications

OBJECTIVETo explore the risk factors, and control measures of cytomegalovirus (CMV) infection after hematopoietic stem cell transplantion (HSCT) in children with primary immunodeficiency diseases(PID).

METHODSWe retrospectively analyzed results of 26 patients with PID-Wiskott-Aldrich syndrome (WAS, n=20), severe combined immunodeficiency (SCID, n=1) , X-linked chronic granulomatous disease (XCGD, n=2) and X-linked hyper-immunoglobulin M (IgM) syndrome (XHIM, n=3)-who underwent HSCT from June 2007 to December 2012 in our center. Serologic studies (ELISA) and weekly CMV infection surveillance (quantitative PCR, qPCR) were routinely performed before and after HSCT. Ganciclovir or forcarnet was used for pre-emptive and curative therapy.

RESULTSAll 26 patients were male with the median age at HSCT of 27 months (range 7-77 months). At a median follow up of 24 months (range 5-66 months), the 5-year overall survival rate was (75.0 ± 9.0) %. CMV infection occurred in 42.3% (11 of 26) of the patients, two of them developed CMV interstitial pneumonia (CMVIP). Univariate analysis revealed that the incidence of pre-transplant CMV infection between with and without CMV activation groups after HSCT was significantly different (62.5% vs 10.0%, P=0.010). Additional variables not associated with CMV infection were stem-cell sources, donor type, HLA disparity and acute GVHD (all P values>0.05).

CONCLUSIONCMV infection was a major complication of HSCT. Sensitive monitoring, early diagnosis, timely treatment may improve the survival rate for these PID undergoing HSCT.

Child ; Child, Preschool ; Cytomegalovirus Infections ; virology ; Graft vs Host Disease ; Granulomatous Disease, Chronic ; therapy ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Infant ; Male ; Retrospective Studies ; Risk Factors ; Severe Combined Immunodeficiency ; therapy ; Tissue Donors ; Wiskott-Aldrich Syndrome ; therapy

During the past decades, there has been a great evolution in the field of fetal therapy for congenital defects. Prenatal screening or diagnostic methods including non-invasive and invasive methods and fetal ultrasound have led to earlier and more accurate diagnosis of congenital anomalies. Recent advances in several therapeutic techniques including ultrasound-guided needle therapy, laser therapy or fetal endoscopy, have allowed some fetuses at risk with anatomical defects, to be corrected in utero but still, its clinical indications remain limited. Over the last 30 years, many researchers found usefulness of pluripotent stem cells from amniotic fluid and placenta because they are sources of diverse progenitor cell populations called mesenchymal stem cells. In some human conditions like severe combined immunodeficiency syndrome and chronic granulomatous disease, fetal therapy using stem cell replacement showed some promising results in researches but more studies are required to apply in clinical settings. The aim of this article is to summarize a current status and future perspective of stem cell therapy for treatment of congenital fetal anomalies.
Amniotic Fluid ; Congenital Abnormalities ; Diagnosis ; Endoscopy ; Female ; Fetal Therapies* ; Fetus ; Granulomatous Disease, Chronic ; Humans ; Laser Therapy ; Mesenchymal Stromal Cells ; Needles ; Placenta ; Pluripotent Stem Cells ; Prenatal Diagnosis ; Severe Combined Immunodeficiency ; Stem Cells* ; Ultrasonography

BACKGROUND: Mesenchymal stromal cells (MSCs) have potent immunomodulatory and neuroprotective properties, and have been tested in neurodegenerative diseases resulting in meaningful clinical improvements. Regulatory guidelines specify the need to perform preclinical studies prior any clinical trial, including biodistribution assays and tumourigenesis exclusion. We conducted a preclinical study of human bone marrow MSCs (hBM-MSCs) injected by intrathecal route in Non-Obese Diabetic Severe Combined Immunodeficiency mice, to explore cellular biodistribution and toxicity as a privileged administration method for cell therapy in Friedreich's Ataxia. METHODS: For this purpose, 3 × 10⁵ cells were injected by intrathecal route in 12 animals (experimental group) and the same volume of culture media in 6 animals (control group). Blood samples were collected at 24 h (n = 9) or 4 months (n = 9) to assess toxicity, and nine organs were harvested for histology and safety studies. Genomic DNA was isolated from all tissues, and mouse GAPDH and human β2M and β-actin genes were amplified by qPCR to analyze hBM-MSCs biodistribution. RESULTS: There were no deaths nor acute or chronic toxicity. Hematology, biochemistry and body weight were in the range of normal values in all groups. At 24 h hBM-MSCs were detected in 4/6 spinal cords and 1/6 hearts, and at 4 months in 3/6 hearts and 1/6 brains of transplanted mice. No tumours were found. CONCLUSION: This study demonstrated that intrathecal injection of hBM-MSCs is safe, non toxic and do not produce tumors. These results provide further evidence that hBM-MSCs might be used in a clinical trial in patients with FRDA.
Animals ; Biochemistry ; Body Weight ; Bone Marrow ; Brain ; Cell- and Tissue-Based Therapy ; Culture Media ; DNA ; Friedreich Ataxia ; Heart ; Hematology ; Humans ; Injections, Spinal ; Mesenchymal Stromal Cells ; Methods ; Mice ; Neurodegenerative Diseases ; Neuroprotection ; Reference Values ; Severe Combined Immunodeficiency ; Spinal Cord