摘要:

We studied a large North American Caucasian population of patients with biopsy proven IgA nephropathy for polymorphisms of HLA-A,B,C, HLA-DR, HLA-DQ and HLA-DP using a combination of serologic phenotyping and polymerase chain reaction sequence specific oligonucleotide probe (PCR-SSOP) hybridization genotyping. We also examined patients for polymorphisms of immunoglobulin by determing Gm and Km allotypes. When compared to healthy local controls there was an apparent decrease in HLA-DR5 (DRw11, DRw12) suggesting that this allele had a protective effect on disease susceptibility. None of the previously reported HLA-DQ associations found among Japanese or British Caucasian patients were found among this large North American Caucasian population. The HLA-DPB1*0601 genotype was increased among patients, but this was not significant when corrected for multiple comparisons. There were no differences in the distribution of Gm or Km allotypes among patients versus controls, regardless of whether they were stratified into those with progressive or non-progressive renal disease. Taken together, these findings suggest that there is substantial genetics heterogeneity in susceptibility to IgA nephropathy among different ethnic and/or geographically distinct populations.

ISSN:0891-6934    

DOI:10.3109/08916939409008002

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Rabbits immunized with polylysine-polyglutamate complex induced high titer antibodies. The immune IgG exhibited high degree of specificity towards the immunogen. In a competition assay, nDNA, heat denatured DNA and total buffalo thymus RNA were inhibitory. An appreciable binding with polyglutamate, poly(rG). poly(dC) poly(dG). poly(dC), cardiolipin, poly(dA-dU). Poly(dA-dU) and Z-or Z-like conformations demonstrates the polyspecificity of induced antibodies. The immunological specificity of induced antibodies was comparable to autoantibodies derived from SLE. The results might be of some help in undcrstanding the etiology of autoimmune process.

ISSN:0891-6934    

DOI:10.3109/08916939409008003

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

We investigated the expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) by cells in the central nervous system (CNS) of Lewis rats during acute experimental allergic encephalomyelitis (EAE). A few endothelial cells in the CNS of normal rats expressed ICAM-1, whereas during the active phase of EAE, ICAM-1 was present on many endothelial cells. This alteration was detectable the day before clinical symptoms. Sincc histopathological studies showed few detectable mononuclear cells or inflammatory foci in any section of the preclinical rats, the expression of ICMA-1 was considered to be important at least in the early stage of inflammation. LFA-1 was seen on perivascular infiltrating cells. An increase in either ICAM-1- or LFA-1-positive cells was initially seen in the lumbosacral portion of the spinal cord, which then extended to the thoracic portion. The number of either ICAM-1- or LFA-1-positive cells peaked on the day of clinical onset in the lumbosacral portion. In contrast, in the thoracic portion, a peak in the number of either ICAM-1- or LFA-1-positivc cells was observed on the day after clinical onset. This ascending extension of either ICAM-1- or LFA-1-positive cells was correlated with the progression of neurologic signs. It is suggested that increased expression of ICAM-1 and LFA-1 in the CNS of rat EAE may promote the extravasation of lymphocytes across the blood-brain barrier and be related to progression of the disease.

ISSN:0891-6934    

DOI:10.3109/08916939409008004

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Circulating immune complexes (ICs) containing the pancreatic antigen against SP3–1 monoclonal antibody were measured in patients with idiopathic chronic pancreatitis (ICP) and Sjögren syndrome (SjS) by Raji cell and solid-phase radioimmuno-assays (RIA). The mean serum levels of ICs measured by solid-phase RIA were significantly higher in patients with ICP (n = 23) and SjS (n = 21) than control (n = 15, p<0.05, p<0.02, respectively). ICs were positive in 10 patients with ICP (43%) and 12 SjS patients (57%). Raji cell assay also revealed a significantly higher serum ICs levels in patients with ICP (n = 17) and SjS (n = 12) compared with those of control (n = 7, p<0.025, p<0.005, respectively). Seven patients with ICP (41%) and 8 SjS patients (67%) had positive ICs. This was in contrast to the normal level of ICs in patients with alcoholic chronic pancreatitis, primary biliary cirrhosis, and chronic thyroiditis. Our analysis demonstrated a significant and positive relationship between RIA and Raji cell assay (r = 0.70, p<0.05). Our results suggest that ICs specific for SP3–1 may play a role in the pathophysiology of ICP and SjS.

ISSN:0891-6934    

DOI:10.3109/08916939409008005

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

We reported a patient who gave birth to 3 children with transient neonatal hypothyroidism. She had 3 different antibodies (Ab) to the thyrotropin receptor (TSHR) in her serum, viz., TSH binding-inhibiting (TBIAb), thyroid-stimulating (TSAb) and an additional stimulating Ab (SAb). The SAb differed from TSAb in that itsin vitrostimulating effect in human thyroid and FRTL5 cells was not inhibited by TBIAb [similar data now obtained with Chinese hamster ovary (CHO) cells transfected with cloned human TSHR]. Because of symptomatic goiter enlargement the patient underwent subtotal thyroidectomy. About 50% of the gland was infiltrated with lymphocytes; thyroid follicles had columnar epithelium, despite suppression of TSH by thyroxine and the presence of the potent TBIAb. Fifteen months later, when all 3 Ab showed a decline of∼3 fold, she gave birth to hypothyroid twins. These data support the following conclusions: 1) thyroidectomy and immunosuppression of pregnancy do not prevent neonatal thyroid disease if TSHR Ab (TRAb) are of high titer; 2) the thyroid is not a major site of TRAb production; 3) SAb is a thyroid stimulator, distinct from TSAb in that it does not share binding epitopes on the TSHR with either TSH or TBIAb; 4) SAb was the probable cause of thyroid growth in this patient.

ISSN:0891-6934    

DOI:10.3109/08916939409008006

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Several questions exist regarding CD5+B cells. These include the ability of these cells, as compared to CD5−B cells, to undergo an Ig isotype class switch, the subclasses utilized, and the effects that switching may have on antigen binding. To address these issues, ten patients with chronic lymphocytic leukemia (CLL) whose CD5+leukemic B cell clones produced IgG were studied. Monoclonal IgG was collected from PMA-stimulated CLL cells and from heterohybridomas constructed with these cells, and then analyzed for IgG subclass utilization, autoreactivity, and DNA idiotype expression.The monoclonal B cells from 80% of the CLL patients produced IgC1 and those from 20% produced IgG3. None produced IgG2. In contrast to the known autoreactivity of IgM-producing CD5+CLL cells (>50% autoreactive), none of these IgG antibodies reacted significantly with the autoantigens tested. However, three did react significantly with autoantigen after artificially increasing antibody valency by crosslinking. Whereas five of the IgG molecules expressed a cross reactive idiotypic (CRI) marker characteristic of non-mutatedκanti-DNA antibodies, three expressed a CRI displayed primarily on mutated IgG anti-DNA antibodies.Thus, some CD5+human B cells can undergo an isotype class switch that for these CLL cells is biased against IgG2 and in favor of the IgG1 and IgG3. In their native state the IgG molecules secreted by these isotype-switched CD5+cells have diminished autoreactivity, as compared to IgM-producing CLL cells. Since some of the IgG antibodies could be made auto- and poly-reactive by increasing antigen-binding valency, while others expressed idiotypic markers of mutated antibodies, certain of these CD5+B cells probably utilize non-mutated Ig V genes coding for polyreactive antibodies, whereas others may use genes that have undergone somatic mutation and that code for more restricted specificities. Therefore, both valency and VHgene mutation may account for the diminished autoreactivity of these CD5+B cell-derived IgG antibodies.

ISSN:0891-6934    

DOI:10.3109/08916939409008007

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

HLA class II alleles in the DQA1, DQB1, DRB1, and DPB1 genes were investigated in Japanese patients with myasthenia gravis (MG) by digestion of polymerase chain reaction amplified DNAs with allele specific restriction endonucleases (PCR-RFLP). A significantly higher frequency of DQB1*03, which includes *0301, *0302, *0303 and determines the serological DQ3 specificity, was observed in feamle patients less than 30 years in age at onset of disease compared with healthy controls (90.5 vs. 53.2%). This study also confirms the high incidence of DPB1*0201 in early-onset female patients compared to the controls (85.7 vs. 40.3%). Moreover, 81.0% of the early onset female patients were found to carry both DQB1*03 and DPB1*0201, compared to 17.7% of the controls. Since DQB1*03 and DPB1*0201 are not in linkage disequilibrium, both these alleles are supposed to be synergistically involved in disease development in early-onset female MG. In contrast, no obvious association of HLA-DQA1, DQB1, DRB1 and DPB1 alleles with either late-onset patients or patients with thymoma was observed. Clearly, the genetic background of Japanese females with early onset MG is different from that of other patients with MG.

ISSN:0891-6934    

DOI:10.3109/08916939409008008

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

We investigated whether thyroglobulin (TG) autoantibodies (aAb) cross-react with thyroperoxidase (TPO) through an idiotypic structure using pooled normal human IgG (NhIgG) as a natural anti-idiotype reagent. Affinity-purified TG aAb from pooled IgG of patients with autoimmune thyroid disease were chromatographed on Sepharose-bound NhIgG. About one fourth of the loaded material bound to and eluted from the coupled gel. Eluted TG aAb were found reactive to TG and TPO and their TPO but not TG binding was strongly inhibited by molar excess of NhIgG. These TG aAb appeared to be mainly directed to an immunodominant TG antigenic region defined by TG monoclonal antibodies (mAb) from a single cluster of reactivity. These TG mAb were also found to recognize TPO and their binding to TPO but not TG was inhibited by molar excess of NhIgG as already observed with TG aAb. Taken together, these results indicated that TPO interacts with an idiotype present on human TG aAb and mouse TG mAb displaying a similar epitopic specificity; this interspecies idiotype is recognized by anti-idiotype antibodies present in NhIgG. Our results suggest that thyroid autoimmunity can be envisaged, at least in part, as a disturbance in interconnected idiotypic networks.

ISSN:0891-6934    

DOI:10.3109/08916939409008009

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939409008010

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939409008011

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor