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Immunoglobulins, immunoglobulin subclass-distributions and serologic markers in some renal and systemic disorders
Linköping University, Department of Medicine and Care, Nephrology. Linköping University, Faculty of Health Sciences.
2000 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In this study we evaluated pathogenetic factors and possible mediators of renal and systemic disorders where immunologic mechanisms might be of importance.

An abberant immunoglobulin and IgG-subclass distribution was detected in 103 patients with primary and secondary glomerulonephritis as well as in 38 patients with the systemic disease primary Sjögren 's syndrome or purpura hypergammaglobulinemica (elevated IgG1 and low IgG2 ).

The drug hydralazine, an anti-hypertensive, was considered to cause renal disease on an immunologic base in 17 patients, with autoantibody production (mainly ANA and antibodies to myeloperoxidase).

Dialysis-patients showed adequate antibody responses to vaccination against pneumococci but low responses against hepatitis B, while the IgG-subclass response of the hepatitis B antibody (anti-HBs) was low, but not shown to be significantly different from that of healthy adults.

A therapeutical removal of igG-antibodies with immunoadsorption or plasmapheresis was considered to have a possible adjuvant effect to medical immunosuppressive treatment alone in 44 patients with rapidly progressive glomerulonephritis.

Hepatitis C virus (HCV) is common in dialysis patients and renal transplant recipients. In 20 anti-HCV positive sera from 1988-91 recombinant immunoblott assay (RIBA) was positive in 8 cases and indeterminate in 7, while HCV RNA was present in 13/20 tested sera. In October 1991 17% of our hemodialysis patients were verified or suspected carriers while 11% were verified or suspected carriers in January 1997. Genotype 2b was found in 13/24 tested cases and in 7 amplifiable 2b sequences a strong phylogenetic relationship occurred. In 8 out of 12 RIBA-3 indeterminate sera HCV-RNA was still positive. Awareness and preventive measures limited transmission between patients.

Indeterminate RlBA-results should, also with modem assays, be regarded with caution due to the relative immunodeficiency of uremic patients.

In conclusion renal and systemic diseases may affect the serum immunoglobulins and immunoglobulin G-subclasses, while a study of the specific antibody subclass distributions (anti-HBs) showed no difference in renal (dialysis) patients and healthy adults. Medication (hydralazine) and infection may be triggering factors of various forms of glomerulonephritis. Uremia affects the antibody responses to hepatitis C in dialysis patients. The extent of renal disease as well as the possibility of therapeutic removal of antibodies is also important for the immunologic responses of such disorders.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 2000. , 87 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 646
Keyword [en]
Immunoglobulins, immunoglobulin-subclass distribution, hydralazine, ANCA, anti-:MPO, primary SjOgren's syndrome, hepatitis B vaccination, anti-HBssubclasses, immunoadsorption, plasmapheresis, antibodies, hepatitis C virus, transmission, recombinant immunoblot assay, hepatitis C genotype
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-27455Local ID: 12108ISBN: 91-7219-747-1 (print)OAI: oai:DiVA.org:liu-27455DiVA: diva2:248007
Public defence
2000-12-15, Berzeliussalen, Universitetssjukhuset, Linköping, 13:00 (Swedish)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-08-15Bibliographically approved
List of papers
1. Serum immunoglobulins and IgG subclasses in patients with glomerulonephritis
Open this publication in new window or tab >>Serum immunoglobulins and IgG subclasses in patients with glomerulonephritis
1989 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 225, no 1, 3-7 p.Article in journal (Refereed) Published
Abstract [en]

The serum concentrations of IgG, IgA, IgM and of the four subclasses of IgG were determined by radial immunodiffusion in 103 patients, mean age 42 (range 16–72), with various types of glomerulonephritis. Forty-nine healthy blood donors, mean age 41 years (range 19–65), served as controls. Kidney biopsies were obtained from all the patients for examination by histopathology and by immunofluorescence. The glomerulopathies were classified according to WHO criteria.

The serum immunoglobulin patterns were different for the various clinical groups of patients. Patients with Wegener's granulomatosis, rapidly progressive glomerulonephritis and SLE had a significant increase in total IgG and of IgG4 (P < 0.05–0.001). Patients with minimal change disease had low concentrations of IgG (P < 0.001) with a significant decrease in IgG1 and IgG2 (P < 0.001 and 0.01. respectively). Highly significant increases in IgA were noted for patients with IgA nephritis (P < 0.001) but high levels were also seen in patients with chronic glomerulonephritis. The findings might have diagnostic implications.

Keyword
glomerulonephritis, serum immunoglobulins, IgG, subclasses
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-79900 (URN)10.1111/j.1365-2796.1989.tb00028.x (DOI)
Available from: 2012-08-15 Created: 2012-08-15 Last updated: 2017-12-07Bibliographically approved
2. Autoantibodies to leucocyte antigens in hydralazine-associated nephritis
Open this publication in new window or tab >>Autoantibodies to leucocyte antigens in hydralazine-associated nephritis
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1992 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 231, no 1, 37-42 p.Article in journal (Refereed) Published
Abstract [en]

Clinical and laboratory findings and drug history were studied in 17 patients with suspected hydralazine-associated nephritis, five of whom only had renal disease, while twelve also had extrarenal manifestations. Renal biopsies revealed extracapillary proliferative or focal segmental proliferative glomerulonephritis in 10 patients, and tubulo-interstitial nephritis in five patients. Antinuclear antibody (ANA) was found in 16 patients, but none of the 14 patients tested had antibodies to DNA. Tests for antibodies to myeloperoxidase (anti-MPO) and antibodies to neutrophil cytoplasm antigen (ANCA) were performed by ELISA. Twelve of the 14 patients tested had anti-MPO; five of these 14 patients had ANCA, while one had borderline levels. These findings suggest that hydralazine facilitates the induction of a systemic disease with multiple autoantibody production.

Keyword
ANA, ANCA, anti-MPO, hydralazine, systemic lupus erythematosus, vasculitis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-79903 (URN)10.1111/j.1365-2796.1992.tb00496.x (DOI)
Available from: 2012-08-15 Created: 2012-08-15 Last updated: 2017-12-07Bibliographically approved
3. IgG2 deficiency in primary Sjögren's syndrome and hypergammaglobulinemic purpura
Open this publication in new window or tab >>IgG2 deficiency in primary Sjögren's syndrome and hypergammaglobulinemic purpura
1994 (English)In: Clinical Immunology and Immunopathology, ISSN 0090-1229, E-ISSN 1090-2341, Vol. 70, no 1, 60-65 p.Article in journal (Refereed) Published
Abstract [en]

Total IgG and IgG subclasses were studied in 34 patients with primary Sjogren's syndrome and 4 with hypergammaglobulinemic purpura. Total IgG was elevated in 30/34 patients with Sjogren's syndrome. IgG1 increase was responsible for the main part of total IgG increase, contrasting with low levels of IgG2. The difference in IgG1/IgG2 ratio between 38 patients as a group and 40 normal controls was statistically highly significant, but was not seen in all patients. Six patients had markedly low levels of IgG2, but only two had severe repeated respiratory infections. These observations probably reflect selective autoantibody restiction to the IgG1 subclass. We conclude that patients with Sjogren's syndrome may be IgG2 subclass deficient despite elevated levels of total IgG, but also that such deficiency in most instances does not cause a tendency to infections. IgG subclass analysis may be of value to characterize polyclonal IgG increase, since IgG1 subclass predominance often indicates autoimmune disease.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-79906 (URN)10.1006/clin.1994.1011 (DOI)
Available from: 2012-08-15 Created: 2012-08-15 Last updated: 2017-12-07Bibliographically approved
4. The Immunoglobulin G Subclass Response to Hepatitis B Vaccine and the Antibody Response to Pneumococcal Polysaccharides in Dialysis Patients
Open this publication in new window or tab >>The Immunoglobulin G Subclass Response to Hepatitis B Vaccine and the Antibody Response to Pneumococcal Polysaccharides in Dialysis Patients
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

We examined the response to hepatitis B vaccination in dialysis patients, and evaluated our vaccination program to hepatitis B virus. No new cases of hepatitis B occurred during the study period, i.e. from 1980 and onwards. Sera were analyzed for anti-HBs in 25 dialysis patients vaccinated at least three times against hepatitis B and 53 health care staff vaccinated three times. The IgG subclass distribution of antibodies to hepatitis B surface antigen (anti-HBs) was determined in 11 dialysis patients and in 45 healthy controls. The antibody response to pneumococci was determined in 29 vaccinated patients.

Results: Ten of 25 (40%) of the dialysis patients had anti-HBs when both tests after the third and/or fourth injections were considered. In four patients a fourth injection was cancelled due to transplantation or bad health, while such data were lacking in 8 cases. In staff 49/53 (93%) of the persons responded with anti-HBs production. In anti-HBs positive patients and controls a significant difference in the response of healthy adults was observed in anti-HBs IgG 1 (p<0.001) vs all other IgG subclasses. Dialysis patients had low levels, or negative findings, in all cases, with lgGI as the highest proportion found (3/11 patients). An antibody response to pneumococcal vaccination was registred in 25 out of 29 dialysis patients (in all 86 %).Dialysis patients respond poorly to hepatitis B vaccine. An anti-HBs subclass response mainly restricted to IgG I was observed in healthy adults, while dialysis patients had low or negative test results affecting all subclasses.

The findings suggest a general deficit in the ability to produce anti-HBs rather than a deficit in the production of a specific subclass of this antibody. Moreover, RBV-vaccination schedules in renal transplant recipients should be started early, as some patients otherwise, due to transplantation or bad health, may not receive a fourth injection.

The antibody response to pneumococcal vaccination indicates that the antigen involved is important in vaccination responses in dialysis patients.

Keyword
Antibodies, dialysis, hepatitis B virus, Immunoglobulin G, pneumococci, vaccination.
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-79909 (URN)
Available from: 2012-08-15 Created: 2012-08-15 Last updated: 2012-08-15Bibliographically approved
5. Plasma exchange or immunoadsorption in patients with rapidly progressive crescentic glomerulonephritis: A Swedish multi-center study
Open this publication in new window or tab >>Plasma exchange or immunoadsorption in patients with rapidly progressive crescentic glomerulonephritis: A Swedish multi-center study
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1999 (English)In: International Journal of Artificial Organs, ISSN 0391-3988, E-ISSN 1724-6040, Vol. 22, no 2, 81-87 p.Article in journal (Refereed) Published
Abstract [en]

A therapeutic removal of antibodies may be achieved by immunoadsorption (IA) or by plasma exchange (PE). The aim of this prospective randomised study was to compare the efficacy of these different techniques with regard to treatment of patients with rapidly progressive glomerulonephritis (RPG) having at least 50% crescents. Forty-four patients with a RPG were included for treatment either by IA or PE (with albumin as substitution for removed plasma). All patients were additionally treated with immunosuppression. A median of 6 sessions of PEs were performed in 23 patients compared with 6 IAs in 21 patients. Goodpasture's syndrome (GP) was present in 6 patients (PE 3, IA 3). All of them started and ended in dialysis, two died. Among the remaining 38 patients (26 men, 12 women) 87% had antibodies to ANCA. Creatinine clearance for PE versus IA were at a median at start 17.1 and 19.8 ml/min, and at 6 months 49 and 49 ml/min, respectively. At 6 months 7 of 10 patients did not need dialysis (remaining: IA 0/5 and PE 2/5, n.s.). The extent of improvement did not differ between the groups. Three patients died during the observation period of 6 months (IA 2; PE 1, on HD). Although no difference was found between the IA or the PE group this study shows that the protocol used was associated with an improved renal function in most patients (except for Goodpasture's syndrome) whereas 70% of them could leave the dialysis program.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25801 (URN)10212042 (PubMedID)10238 (Local ID)10238 (Archive number)10238 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
6. Detection and prevention of hepatitis C in dialysis patients and renal transplant recipients: A long-term follow up (1989–January 1997)
Open this publication in new window or tab >>Detection and prevention of hepatitis C in dialysis patients and renal transplant recipients: A long-term follow up (1989–January 1997)
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2002 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 251, no 2, 119-128 p.Article in journal (Refereed) Published
Abstract [en]

Background. Hepatitis C is frequent problem in dialysis wards.

Design.  A long time (1989–97) follow up of hepatitis C virus (HCV) infection in a Swedish nephrology unit was performed with anti-HCV screening, confirmatory antibody tests, viral RNA detection and molecular characterization. Case histories were reviewed with focus, onset of infection, liver morbidity and mortality.

Results.  In October 1991, 10% (19 of 184) of the patients in the unit (haemodialysis-, peritoneal dialysis and transplanted patients) were verified or suspected HCV carriers, whilst the number at the end of 1996 was 8% (13 of 157). Most patients were infected before 1991 but only in one case from a known HCV-infected blood donor. No new HCV infections associated with haemodialysis occurred during the study period. A total of 13 of 24 viremic patients had HCV genotype 2b, a pattern suggesting nosocomial transmission. This was further supported by phylogenetic analysis of HCV viral isolates in seven. HCV viremia was also common in patients with an incomplete anti-HCV antibody pattern as 8 of the 12 indeterminant sera were HCV-RNA positive.

Conclusions.  Awareness, prevention, identification of infected patients and donor testing limited transmission. Indeterminant recombinant immunoblot assays (RIBA)-results should be regarded with caution as a result of the relative immunodeficiency in uremic patients. Our data indicate nosocomial transmission in several patients.

Keyword
dialysis, hepatitis C virus, polymerase chain reaction, recombinant immunoblot assay, transmission
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-26424 (URN)10.1046/j.1365-2796.2002.00938.x (DOI)10966 (Local ID)10966 (Archive number)10966 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved

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