Subject(s)
Combined Modality Therapy/methods , Immunoglobulin E/blood , Leukemia, Lymphocytic, Chronic, B-Cell , Lymph Nodes/pathology , Skin Diseases, Vascular , Vasculitis , Adult , Antineoplastic Protocols , B-Lymphocytes/immunology , Biopsy/methods , Female , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Leukemia, Lymphocytic, Chronic, B-Cell/immunology , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Leukemia, Lymphocytic, Chronic, B-Cell/therapy , Positron-Emission Tomography/methods , Skin Diseases, Vascular/diagnosis , Skin Diseases, Vascular/etiology , Skin Diseases, Vascular/physiopathology , Skin Diseases, Vascular/therapy , Tomography, X-Ray Computed/methods , Treatment Outcome , Vasculitis/diagnosis , Vasculitis/etiology , Vasculitis/physiopathology , Vasculitis/therapyABSTRACT
The ability to generate inducible pluripotent stem cells (iPSCs) and the potential for their use in treatment of human disease is of immense interest. Autoimmune diseases, with their limited treatment choices are a potential target for the clinical application of stem cell and iPSC technology. IPSCs provide three potential ways of treating autoimmune disease; (i) providing pure replacement of lost cells (immuno-reconstitution); (ii) through immune-modulation of the disease process in vivo; and (iii) for the purposes of disease modeling in vitro. In this review, we will use examples of systemic, system-specific and organ-specific autoimmunity to explore the potential applications of iPSCs for treatment of autoimmune diseases and review the evidence of iPSC technology in auto-immunity to date.
ABSTRACT
OBJECTIVE: To establish gene copy number (GCN)-specific normal ranges for serum C4 genes and to determine their utility with respect to the interpretation of chronically low serum C4 concentrations in patients with clinically quiescent systemic lupus erythematosus (SLE). METHODS: C4 serum concentrations were estimated by automated turbidimetry, and C4 GCNs were determined using the TaqMan real-time polymerase chain reaction (PCR) analysis in 184 unselected individuals and in 10 patients with type 1 diabetes mellitus (DM) who were selected for the presence of only 2 copies of the C4 gene. C4 GCNs were also determined in 11 patients with clinically quiescent SLE who had chronically low serum C4 concentrations. RESULTS: A total of 33% of the variation in serum C4 concentrations could be accounted for by both C4A and C4B GCNs (R(2) = 0.30, P ≤ 0.0001). There was a median of 2 gene copies at the C4A locus (53.8%) and 2 at the C4B locus (58.7%). The median total number of C4 genes was 4 (55.4%). C4 GCN-specific normal ranges were established. A chronically low serum C4 concentration was explained by a low C4 GCN in 3 of 11 patients tested. CONCLUSION: This study establishes the feasibility of establishing C4 GCN-specific normal ranges using the TaqMan real-time PCR assay. Chronically low serum C4 concentrations in SLE patients are sometimes explained by low C4 GCNs.
Subject(s)
Complement C4/genetics , Gene Dosage , Genetic Predisposition to Disease , Lupus Erythematosus, Systemic/genetics , Adult , Aged , Alleles , Complement C4/metabolism , Female , Genotype , Humans , Lupus Erythematosus, Systemic/blood , Male , Middle Aged , Reference ValuesABSTRACT
A 63-year-old man was admitted for investigation of blurred vision and multiple ring-enhancing lesions on cranial MRI. Histopathological examination of tissue obtained at brain biopsy showed multiple Toxoplasma gondii cysts. He was started on a combination of sulphadiazine and pyrimethamine for cerebral toxoplasmosis and was subsequently diagnosed with HIV-1 infection. He then developed acute renal failure and flank pain and was diagnosed with bilateral vesico-uretric calculi requiring bilateral stent insertion. The retrieved renal calculi were negative for the common stones that are routinely tested for in our laboratory and had the macroscopic characteristics of a sulphadiazine stone. His renal failure responded to cessation of the sulphadiazine.
