[Clinical findings and diagnosis of Yersinia enterocolitica infections; a retrospective study in Friesland].
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Humans↗
Biomedical subjects
T E Feltkamp
Publications and source records attributed to T E Feltkamp.
HLA-B27 as a receptor for cytomegalovirus.
Acute anterior uveitis (AAU) is strongly associated with the genetic marker and cell membrane protein HLA-B27. Although also other genetic factors must play a pathogenetic role, the HLA-class I molecule B27 is up to now the only hold. The normal task of HLA class I molecules is to present endogenous, mostly viral, peptides to receptors on cytotoxic T cells. It is possible that HLA molecules at the cell surface serve as viral receptors. Human cytomegalovirus (HCMV) particles have been found to bind beta 2m. This might promote infectivity by a binding to HLA alpha-chains on cell membranes. We studied this mechanism using mouse fibroblasts transfected for human HLA class I molecules. Susceptibility of these cells for HCMV was compared by measuring of HCMV immediate early antigen (IEA) expression. Earlier we observed that cells transfected with HLA-B27 alpha-chains and beta 2m were significantly more infected than cells expressing HLA-A2 + beta 2m or HLA-B7 or HLA-B27 without beta 2m. However, studying another four, separately transfected, cell lines, all expressing HLA-B27 and beta 2m, three of the five B27 cell lines showed low IEA levels. The degree of infectivity was independent of the degree of B27 expression. These results do not support the previous suggestion that HLA-B27 might act as an HCMV receptor.
Animals↗
Antibodies to a 15 kD nuclear antigen in patients with juvenile chronic arthritis and uveitis.
Young girls with a pauciarticular onset of juvenile chronic arthritis and circulating antinuclear antibodies are at risk for chronic uveitis. The actual nuclear antigen for these antinuclear antibodies has not been defined. Conventional laboratory techniques, such as counter immunoelectrophoresis, have shown that antibodies to well defined "extractable nuclear antigens" (eg, RNP, Sm, SS-A, and SS-B) are not present in patients with juvenile chronic arthritis. Therefore, other, previously unknown nuclear antigens may be involved. Sera of 64 patients with juvenile chronic arthritis, including 22 patients with chronic anterior uveitis, were studied using the immunoblotting technique to characterize the nuclear antigens. Antinuclear antibodies were present in 12 (55%) of the 22 patients with uveitis, and only in six (14%) of the 42 patients without chronic anterior uveitis. With the immunoblotting technique, antibodies to a 15 kD nuclear antigen were found in 10 (45%) of the 22 patients with chronic anterior uveitis, whereas only two (5%) of the 42 patients without chronic anterior uveitis showed these antibodies (P less than 0.001). Only clearly visible and reproducible lines in the immunoblotting patterns were studied. This may provide a diagnostic tool for the early detection of uveitis and means for further pathogenetic studies.
Adolescent↗
Sjögren's syndrome in relation to other autoimmune diseases.
Autoimmune diseases can be divided into primary autoimmune diseases, in which the immune system is over-reactive, leading to an oligoclonal B cell stimulation, and secondary autoimmune diseases, in which the immune system is completely normal but some autoantigens are slightly altered, and are thus considered to be foreign. Sjögren's syndrome probably has characteristics of both types of autoimmune disease. The primary autoimmune diseases can be divided into organ-specific autoimmune diseases like thyroiditis, gastritis and adrenalitis, and generalised autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. Sjögren's syndrome has characteristics of both types of primary autoimmune disease, and therefore occupies a central position among the other autoimmune diseases. The focal position of the disease in the present issue of The Netherlands Journal of Medicine is because of the symposium organized for the occasion of the fifth anniversary of the "Dutch Association of Patients with Sjögren's Syndrome", of which this issue is the report.
Autoimmune Diseases↗
Expression of HLA class I heavy chains and beta 2-microglobulin does not affect human cytomegalovirus infectivity.
Human cytomegalovirus (HCMV) purified from urine or tissue culture supernatant has been reported to contain beta 2-microglobulin (beta 2m), which forms the light chain of HLA class I molecules. It has been postulated that HCMV covered with beta 2m binds to HLA class I alpha-chains at the cell surface. In the present study we used transfected human and mouse cell lines expressing distinct allelic forms of HLA class I and beta 2m to determine whether HLA class I molecules could act as cellular receptors for HCMV. The susceptibility of cells to HCMV infection was estimated by calculating the percentage of cells expressing HCMV immediate early antigens. Although the results showed some variation between different transfected cell clones, no correlation was found between expression of HLA class I on the cell membrane and HCMV infection. Preincubation of HLA class I-positive cells with antibodies against HLA class I antigens inhibited HCMV infection after binding and adsorption of HCMV. Trypsin prevented HCMV infection of both class I-positive and class I-negative cells. We conclude that these results do not support the assumption that HLA class I molecules are functional receptors for HCMV.
Alleles↗
The lifetime cumulative incidence of acute anterior uveitis in a normal population and its relation to ankylosing spondylitis and histocompatibility antigen HLA-B27.
The lifetime cumulative incidence of acute anterior uveitis (AAU) was determined in a sample of a large population (n = 10,500). Nine hundred seventeen subjects, who answered the question "Have you ever had a red eye" in the affirmative in 1977, were asked to participate in a follow-up study 10 years later. From the 917 respondents, 539 were studied completely. A questionnaire was used to collect historic data, and confirmation of these data was obtained from the treating ophthalmologists and physicians. From these data, subjects were selected for an ophthalmologic examination. The respondents also underwent a rheumatologic examination. The results revealed that the lifetime cumulative incidence of definite AAU is approximately 0.2% in the general population and 1% in the histocompatibility antigen HLA-B27-positive population. In one third of the definite AAU patients, the cause of the disease was known. The lifetime cumulative incidence of definite AAU of unknown cause was 0.15% in the general population. When possible and probable AAU are included, the lifetime cumulative incidence of AAU in the general population is about 0.4%. The observed frequency of the concurrence of AAU and ankylosing spondylitis (AS) was 0.4% in the HLA-B27-positive population and 0.02% in the HLA-B27-negative population. Comparison with the expected frequency of the concurrence of AAU and AS revealed that AAU and AS probably are related diseases irrespective of the association of both diseases with HLA-B27.
Acute Disease↗
Acute anterior uveitis and HLA-B27.
All studies among acute anterior uveitis patients (AAU) agree on the importance of and high association with HLA-B27. However, the majority of the HLA-B27+ population will never develop AAU. The partial association of AAU and HLA-B27 is probably not based on a preferential association with a particular B27 subtype, since the HLA-B27 subtypes are equally distributed among normal controls and AAU patients. Therefore, other factors increase the susceptibility to HLA-B27 associated diseases. Family investigations among the relatives of AAU and AS patients suggest the existence of other pathogenic genetic factors in addition to HLA-B27. Due to extensive research, associations with other genes on chromosome 6 could almost be excluded and associations with genes on other chromosomes were not yet found. The only reproducible association between AAU and any genes or gene products is, at the moment, still the association with HLA-B27. However, its role, which most probably is functional, is far from clear.
Acute Disease↗
HLA and uveitis.
The association between HLA-A29 and birdshot chorioretinopathy is the strongest of all associations between HLA and disease. Determination of HLA-A29 is even of diagnostic significance. The association between HLA-B27 and acute anterior uveitis (AAU) is much weaker, but B27 positive AAU may be considered as a distinct clinical entity. B27 positive patients with AAU should be referred to a rheumatologist, because half of these patients have ankylosing spondylitis or Reiter's syndrome. The determination of HLA-Bw51 is of limited but significant diagnostic value for the diagnosis of Behçet's disease. The present article shows how HLA determinations can serve as diagnostic tests. It is explained how the sensitivity and specificity of such tests can be used to calculate the influence of positive or negative results on the probability of the diagnosis. The structure and function of HLA class I molecules is now known to a great extent. This may lead to a better understanding of the pathogenic role of HLA-A29, HLA-B27, HLA-Bw51 and other HLA molecules which are associated with uveitis.
Behcet Syndrome↗
Standards for ANA and anti-DNA.
A review of the history, production, characterics and availability of the standards and reference preparations in the field of ANA determination is given. For ANA of the homogeneous type and for anti-DNA standard reagents are recognized by the WHO. This enables the expression of quantitative results in international units, leading to a decrease of interlaboratory variations. For the other types of nuclear fluorescence and for anti-Sm, anti-Ro (SS-A), anti-La (SS-B), anti-Scl 70 and anti-Jo-1, reference reagents are made available by the Arthritis Foundation (AF) and the Centers for Disease Control (CDC) in the USA. For anti-nRNP, a WHO reference reagent exists. The use of the above materials is advocated. Requests for WHO standards should be directed to: Dept. of Reagents CLB, P.O. Box 9190, 1006 AD Amsterdam, The Netherlands, and for AF/CDC reagents to: AF/CDC ANA Ref. Lab., Immunology 1 - 1202 A 25, CDC, Atlanta GA 30333, USA.
Antibodies, Anti-Idiotypic↗
Ophthalmological significance of HLA associated uveitis.
The association between HLA-A29 and birdshot chorioretinopathy is the strongest association between HLA and disease ever described. The determination of HLA-A29 is therefore of diagnostic significance. The association between HLA-B27 and acute anterior uveitis (AAU) is much weaker. However, it is evident that B27+ AAU is clinically different from B27-AAU. Half of the B27+AAU patients have or will have ankylosing spondylitis or Reiter's syndrome. The determination of HLA-B27 is therefore of clinical significance and should be determined in each case of AAU. The B27+ patients should be referred to a rheumatologist. The determination of HLA-Bw51 is of limited but significant diagnostic value for the diagnosis of Behçet's disease in countries around the Mediterranean Sea or Japan. In Northern Europe HLA-Bw51 determination will not give much practical information. The structure and function of HLA class I molecules is now known. It is probable that HLA-A29 and HLA-B27 molecules are directly involved in the pathogenesis of respectively birdshot chorioretinopathy and AAU.
Acute Disease↗
HLA-B27 and acute anterior uveitis.
This article reviews the ophthalmological significance of the association between HLA-B27 and acute anterior uveitis (AAU). HLA-B27 determination should be performed in all cases of acute anterior uveitis (AAU), since B27+ AAU is a distinct kind of uveitis. All B27+ AAU patients have to be referred to a rheumatologist because half of these patients has ankylosing spondylitis or Reiter's syndrome. The structure and physiological role of HLA-class I molecules is now known. It is probable that the role of HLA-B27 in the pathogenesis of AAU will be revealed in the coming years.
Acute Disease↗
The influence of HLA-B27 on the infectivity of cytomegalovirus for mouse fibroblasts.
It has been reported that CMV particles are covered with host beta 2-microglobulin (beta 2m). Such viral particles possible use HLA class I alpha-chains as receptors. We could however not reproduce these findings, since beta 2m was not found on CMV particles using electron microscopy. Furthermore, preincubation of target cells with antibodies to HLA class I molecules did not impair infectivity. Performing such experiments it was noted that HLA-B27 transfected mouse fibroblasts were more vulnerable for CMV infection than mouse cells transfected with other HLA class I molecules.
Animals↗
Serum levels of beta 2-microglobulin in HLA-B27+ patients with acute anterior uveitis and ankylosing spondylitis.
Serum levels of beta 2m were monitored in 89 HLA-B27+ patients with acute anterior uveitis (AAU) and in their first degree relatives. Serum levels of both patients and relatives were not elevated compared to sex and age matched controls. Neither the activity of the uveitis, nor the presence or absence of ankylosing spondylitis (AS), correlated with beta 2m levels. On the contrary, 6 of 27 HLA-B27- patients with AAU had elevated serum levels of beta 2m. These findings do not confirm previous reports which showed elevated serum levels of beta 2m in patients with AS. A possible role for beta 2m in the pathogenesis of HLA-B27+ AAU and AS is discussed.
Acute Disease↗
[beta 2 microglobulin and the proximal kidney tubules].
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HLA Antigens↗
New views on B27 associated diseases.
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Acute Disease↗
HLA-B27+ acute anterior uveitis and other antigens of the major histocompatibility complex.
Acute anterior uveitis (AAU) is associated with HLA-B27 in 50% of the patients. Although the association between HLA-B27 and AAU is evident, other genetic factors probably also play a pathogenic role. To investigate whether HLA-B27 only serves as a marker gene for genes next to the B-locus, class I and II HLA antigens of 62 HLA-B27+ AAU patients were determined. Increased frequencies were found for HLA-Cw1, Cw2, DR4, DRw12 and DQw3 if the AAU patients were compared with normal controls. However, when the data were compared to a group of HLA-B27+ controls, no differences were observed. The supposed associations were therefore probably due to linkage disequilibrium with HLA-B27. Homozygosity for HLA-B27 seemed not to increase the chance to acquire AAU. HLA-DR4 was present less frequently in AAU patients with ankylosing spondylitis than in AAU patients without this disease. Haplotype analysis of 21 families revealed that not all relatives suffering from AAU shared the HLA-B27+ haplotype with the proband. Of seven relatives suffering from AAU, five carried the same HLA-B27+ haplotype as the proband, one had inherited another HLA-B27+ haplotype and the last one was HLA-B27-. In conclusion, we could not bring forward any reason to suggest that genes on the short arm of chromosome 6--other than HLA-B27--play a role in the pathogenesis of HLA-B27+ AAU.
Acute Disease↗
A familial study of the inheritance of HLA-B27-positive acute anterior uveitis.
To determine whether factors besides HLA-B27 play a pathogenic role in acute anterior uveitis, we examined 152 first-degree relatives of 42 randomly selected HLA-B27-positive acute anterior uveitis patients. Nine relatives, all from different families, had acute anterior uveitis: eight were HLA-B27 positive and one was HLA-B27 negative. The prevalence of acute anterior uveitis in HLA-B27-positive first-degree relatives of HLA-B27-positive acute anterior uveitis patients was 13% (eight of 63). This is significantly more (P less than .0001) than the frequency of 1% in the normal HLA-B27-positive Dutch population. Ankylosing spondylitis was found in four of 38 (11%) HLA-B27-positive family members over the age of 45 years. This is also significantly more than the prevalence of 1% in a normal HLA-B27-positive Dutch population. Of these four relatives with ankylosing spondylitis, three also had acute anterior uveitis. It was remarkable that two of these four relatives had a proband who had no ankylosing spondylitis.
Adolescent↗
Perivascular infiltration in normal skin of patients with rheumatoid arthritis: association with rheumatoid factors and HLA-DR antigens.
The relation between immunohistological findings in biopsy specimens of apparently normal skin, HLA antigens, and rheumatoid factors (RF) was studied in 120 patients with rheumatoid arthritis (RA), selected for treatment with D-penicillamine. Perivascular infiltration (PVI) of more than three mononuclear cells was present in 77 (68%) of 114 patients, accompanied usually by the presence of IgM or C3, or both, in immunofluorescence studies. The number of perivascular cells was associated significantly with the titre of circulating RF. A weak relation of both perivascular cellular infiltration and RF with HLA-DR3 and DR4 did not reach statistical significance. It is concluded that the histological presence of perivascular inflammation is associated mainly with deposition of RF. It is suggested that the first is merely an epiphenomenon of the latter. PVI was not prognostic for the occurrence of the clinical syndrome of rheumatoid vasculitis. For practical purposes skin biopsies do not appear to be useful in the evaluation of individual patients with RA.
Adult↗