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Biomedical subjects

J F Carlquist

Publications and source records attributed to J F Carlquist.

At least 37 records · Page 2Linked to original sources
PubMed1997

A mutation in the methylenetetrahydrofolate reductase gene is not associated with increased risk for coronary artery disease or myocardial infarction.

OBJECTIVES: We sought to determine whether the C677T transition in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with increased risk for coronary artery disease (CAD) or myocardial infarction (MI). BACKGROUND: Elevated plasma homocysteine has been identified as a risk factor for coronary atherosclerosis. Homocysteinemia may result from deficient MTHFR activity. A thermolabile form of MTHFR, associated with a C677T genetic transition, shows reduced activity and may be a risk factor for CAD. METHODS: Blood was withdrawn from patients undergoing coronary angiography, and DNA was extracted by a phenol-chloroform method. Genotyping was done by polymerase chain reaction (PCR) amplification of a 198-base pair segment of the MTHFR gene that brackets nucleotide 677. The amplicon was digested with the HinfI restriction enzyme. Products were visualized after electrophoresis in 1.5% agarose with ethidium bromide. RESULTS: Among 200 patients with a diagnosis of MI, the polymorphic allelic frequency was 33.3%, compared with 32.1% among 554 control subjects (p = 0.68); homozygosity was present in 11.5% of patients and 10.6% of control subjects (p = 0.74, odds ratio [OR] 1.09, 95% confidence interval [CI] 0.63 to 1.82). Among 510 patients with severe CAD (>60% stenosis), allelic frequency was 32.0%, compared with 34.8% for 168 subjects without CAD (<10% stenosis, p = 0.33); 11.2% of patients with CAD compared with 13.1% of control subjects were homozygous (p = 0.50, OR 0.83, 95% CI 0.5 to 1.40). CONCLUSIONS: Patients with angiographic evidence of CAD or clinical MI do not show an increased frequency of the C677T transition in the MTHFR gene. Our findings do not support this polymorphism as a risk factor for CAD or MI in a predominantly white, well nourished population of unrestricted age.

Adult↗
PubMed1996

Cytokines and rejection of mouse cardiac allografts.

Graft survival is prolonged by pretransplant transfusion of the graft recipient. It has been postulated that graft rejection is associated with Th1-like cytokines. We tested whether transfusion shifts cytokine production from a Th1-type (gamma-IFN production) to a Th2-type (IL-4 production). Transfusion prolonged cardiac allograft (C3H/HeN donor to a C57BL/6 recipient) survival (10.4+/-0.5 versus 7.2+/-0.2 days for controls, P<0.0001). Splenocyte cultures from nontransfused recipients produced supernatant IFN-gamma concentrations of 13.4+/-1.4 ng/ml upon anti-CD3 stimulation; the same cells produced 32.3+/-3.5 pg/ml IL-4 stimulated with Con A. Spleen cells from transfused animals did not produce gamma-IFN with or without stimulation; (P<0.0001) and produced 21.5+/-3.2 pg/ml IL-4 without stimulation (P<0.0001 compared with controls). C57BL/6 CD8+ lymphocytes isolated from rejected C3H grafts were adoptively transferred (6.7+/-1x10(6)/animal) to pretransfused, C57BL/6 recipients of a C3H graft. Graft survival for these recipients was 7.8+/-0.3 days compared with 10.4+/-0.5 days for recipients pretreated with transfusion only (P<0.005). Transcripts of the gamma-IFN gene were present in unmodified grafts but not in the grafts from transfused recipients given the CD8 cells. In conclusion, transfusion downregulated gamma-IFN production and up-regulated IL-4 production and slowed (but did not abrogate) rejection; CD8 graft-infiltrating cells given adoptively restored normal rejection but not IFN-gamma. Further studies are needed to elucidate the role of cytokines in cardiac allograft rejection.

Adoptive Transfer↗
PubMed1996

Increased incidence of Chlamydia species within the coronary arteries of patients with symptomatic atherosclerotic versus other forms of cardiovascular disease.

OBJECTIVES: The objectives of this study were to test prospectively for an association between Chlamydia and atherosclerosis by comparing the incidence of the pathogen found within atherosclerotic plaques in patients undergoing directional coronary atherectomy with a variety of control specimens and comparing the clinical features between the groups. BACKGROUND: Previous work has suggested an association between Chlamydia pneumoniae infection and coronary atherosclerosis, based on the demonstration of increased serologic titers and the detection of bacteria within atherosclerotic tissue, but this association has not yet been regarded as established. METHODS: Coronary specimens from 90 symptomatic patients undergoing coronary atherectomy were tested for the presence of Chlamydia species using direct immunofluorescence. Control specimens from 24 subjects without atherosclerosis (12 normal coronary specimens and 12 coronary specimens from cardiac transplant recipients with subsequent transplant-induced coronary disease) were also examined. RESULTS: Coronary atherectomy specimens were definitely positive in 66 (73%) and equivocally positive in 5 (6%), resulting in 79% of specimens showing evidence for the presence of Chlamydia species within the atherosclerotic tissue. In contrast, only 1 (4%) of 24 nonatherosclerotic coronary specimens showed any evidence of Chlamydia. The statistical significance of this difference is a p value < 0.001. Transmission electron microscopy was used to confirm the presence of appropriate organisms in three of five positive specimens. No clinical factors except the presence of a primary nonrestenotic lesion (odds ratio 3.0, p = 0.057) predicted the presence of Chlamydia. CONCLUSIONS: This high incidence of Chlamydia only in coronary arteries diseased by atherosclerosis suggests an etiologic role for Chlamydia infection in the development of coronary atherosclerosis that should be further studied.

Aged↗
PubMed1995

Immune response factors in rheumatic heart disease: meta-analysis of HLA-DR associations and evaluation of additional class II alleles.

OBJECTIVES: This study used a meta-analysis to examine HLA-DR frequencies in rheumatic heart disease and prospectively examined other class II allelic disease associations. BACKGROUND: Studies of rheumatic heart disease have reported HLA class II allelic associations, but these are inconsistent. METHODS: A meta-analysis combined all known (n = 10) studies to determine disease risk associated with HLA-DR antigen expression. Meta-analysis of studies grouped by ethnic derivation of subjects was also performed. The present study also examined DQA, DQB and DPB allele frequencies by DNA-based strategies. RESULTS: Meta-analysis showed a significant negative disease association with DR5 (odds ratio [OR] 0.67, p < 0.00003) for all combined studies. Among black patients, DR1 was increased (OR 2.80, p < 0.004); DR6 was increased (OR, 2.03, p < 0.003); and DR 8 was decreased (OR 0.32, p < 0.02). Among Eastern Indian patients, DR3 was increased (OR 2.44, p < 0.00003), with decreased expression for DR2 (OR 0.31, p < 0.00001) and DR5 (OR 0.52, p < 0.05). DR4 was increased among American whites (OR 1.74, p < 0.03), although there was significant heterogeneity among studies of whites. DQA, DQB and DPB allele frequencies were similar for control subjects and patients. CONCLUSIONS: Our findings support an association between major histocompatibility complex class II alleles and risk for rheumatic heart disease. However, heterogeneity in associations was observed among different ethnic and racial groups; regional and temporal differences in streptococcal outbreaks may compound this heterogeneity. Further studies are necessary to elucidate the respective contributions of these variables.

Alleles↗
PubMed1994

Major histocompatibility complex class II gene frequencies by serologic and deoxyribonucleic acid genomic typing in idiopathic dilated cardiomyopathy.

Certain immunologic features associated with idiopathic dilated cardiomyopathy (IDC) suggest an infectious and/or autoimmune etiology. In this regard, an association between the major histocompatibility complex class II allele, DR4, and increased risk for IDC was previously identified. In the present report, 43 additional patients with IDC and 236 control subjects were studied for major histocompatibility class II allele associations. DR alleles were identified by microcytotoxicity. No significant differences between control subjects and patients with IDC were seen, although the frequency of DR4 was increased among patients. DR4 subtyping (n = 9) was performed by "dot blot" hybridization of allele-specific oligonucleotide probes to PCR-amplified genomic deoxyribonucleic acid. The DRB1*0401 and DRB1*0404 alleles were each found in 44% (n = 4) of patients with IDC, and DRB1*0407 was identified in 1 patient (11%). DQ and DP alleles were identified by restriction endonuclease codigestion of polymerase chain reaction-amplified deoxyribonucleic acid. The digested fragments were separated and identified by polyacrylamide gel electrophoresis. Differences between patients and control subjects were observed for DQA1*0501 (11% of patients vs 28% of control subjects, p < 0.05) and DQB1*0201 (13% patients vs 25% control subjects, p < 0.05). A modest difference was noted for DQA1*0301 (35% patients vs 23% control subjects, p = 0.08). These findings suggest a complex immune-related etiology for IDC that cannot be explained solely by the presence or absence of a single class II allele. However, this and other studies continue to implicate genes within the class II region in determining the risk for IDC.

Alleles↗
PubMed1994

Measles immunity in employees of a multihospital healthcare provider.

OBJECTIVE: To assess the potential for nosocomial measles transmission by measuring seropositivity among healthcare workers in Utah. DESIGN: Blood specimens were collected for measurement of measles IgG antibody by enzyme immunoassay (EIA). Individuals with undetectable or equivocal antibody levels were considered at risk for infection. Employees were grouped according to the decade of their birth, and analyses of serological findings were done by the Mantel-Haenszel chi-square test for trend. SETTING: The study was performed in a healthcare organization comprised of six urban and 10 rural hospitals. PARTICIPANTS: Employees (n = 5825) were tested regardless of age, history of disease, or immunization. RESULTS: There were 599 employees (10.3%) who were nonimmune. A trend showing age-related differences in immunity was not noted among employees born prior to 1957 (4.7% nonimmune). However, for employees born after that time, there was a significant age-associated increase in the percentage of susceptible individuals (P = 0.00001). The rate of susceptibility was 8.1% for individuals born between 1957 and 1959, 16.3% for individuals born during the 1960s, and 33.7% for those born in the 1970s. CONCLUSIONS: We concluded that employees born after 1960 represent a material risk for transmission of measles in the hospital setting. Despite the low percentage of susceptibility among those born before 1957, the 144 susceptible individuals in this group also are at risk for measles transmission. Thus, during periods of increased measles prevalence, we would recommend screening all healthcare workers regardless of age and vaccinating those who are susceptible.

Adolescent↗
PubMed1994

Correlation between cellular rejection of cardiac allografts and quantitative changes among T-cell subsets identified by V beta epitope expression.

BACKGROUND: Cellular rejection of an allograft is mediated in part by peripheral blood T cells. We tested the hypothesis that quantitative changes in T-cell subsets can be detected in the peripheral blood and that these changes correlate with rejection. METHODS AND RESULTS: T-cell subset analysis was performed by flow cytometry using monoclonal antibodies recognizing six isotypic epitopes of the T-cell receptor beta-chain variable (V) region. These analyses were done at 7-day (mean) time intervals. Fluctuations within a given subset were determined by dividing the number of positive cells observed by the number of positive cells found on the previous analysis. For healthy volunteers observed over a period of 30 days, 119 of 120 subset ratios (99.2%) fell between 0.5 and 2.0. For patients, 57 of 240 subset ratios (23.8%) fell outside of this range (P < .004, chi 2). The occurrence of the abnormal ratios coincided more closely with cellular rejection (mean +/- SD, 7.7 +/- 6.2 days from a positive biopsy; median, 5 days; range, 0 to 28 days) than did the occurrence of normal subset ratios (mean +/- SD, 14.4 +/- 10.9 days from a positive biopsy; median, 11 days; range, 0 to 44 days; P < .005 by Mann-Whitney U test). Regression analysis confirmed a significant (P < .001, R = .91) temporal association between cellular rejection and abnormal subset fluctuations. No correlation was found between abnormal subset ratios and either vascular rejection or use of high-dose prednisone. CONCLUSIONS: T-cell subset measurement may be a method of noninvasive monitoring of cellular rejection after transplantation and may provide insights into the physiology of graft rejection with the potential for the development of more specific immunosuppressive therapy.

Adult↗
PubMed1994

Histoincompatibility-associated differences in the phenotypes of murine cardiac allograft infiltrating T cells.

Mechanisms of graft rejection may be governed in part by the kind and degree of histocompatibility differences between donor and recipient. Cardiac allograft rejection was studied in three murine models selected to provide disparity at different major histocompatibility complex (MHC), minor lymphocyte stimulating (Mls) and other minor histocompatibility loci. Graft survival for the A.TL to A.TH combination (M3) was significantly longer (median day of rejection 15.0 days) than both the B10.A to AKR (M2) or the C57BL/6 to C3H/HeN (M1) donor-recipient combinations (median days of rejection: 9.0 days and 9.0 days respectively; P < 0.001). The infiltration of grafts by T cells was examined by removal of grafts serially post-transplantation and culturing mechanically disrupted graft tissue with interleukin-2 (IL-2). Recovery of T cells by this method revealed highly reproducible characteristics (kinetic and phenotypic), unique to each donor-recipient combination. Cultures from M1 and M2 grafts had differing CD4/CD8 T-cell ratios at days 2 (1.8 versus 0.7, respectively) and 4 (1.6 versus 0.1, respectively) post-transplantation. The M3 model differed from M2 (at days 4, 8 and 10) and from M1 (at days 8 and 10). At these times, cultures of M3 grafts contained a significantly increased percentage of CD4 cells and significantly decreased percentage of CD8 cells (CD4/CD8 ratios 0.9-1.3) by comparison with M1 (CD4/CD8 ratios 0.02-0.04) and M2 (CD4/CD8 ratios 0.1-0.02). Long-surviving M3 grafts (greater than 30 days post-transplantation) were compared with grafts removed immediately upon cessation of graft function (days 14, 15 and 18 post-transplantation). There was a significant difference between these groups in the ratios of CD4/CD8 T-cell ratios (1.1 versus 0.4, respectively). This study suggests that the cellular rejection mechanism of a graft is a variable process driven by the individual histocompatibility antigen disparity between donor and recipient. These findings may have diagnostic and therapeutic applications in organ transplantation.

Animals↗
PubMed1993

Accelerated rejection of murine cardiac allografts by murine cytomegalovirus-infected recipients. Lack of haplotype specificity.

Clinical studies have revealed a correlation between cytomegalovirus (CMV) infection and acute allograft rejection. Likewise, for a murine model we observed that C3H (H-2k) recipients infected with murine CMV (MCMV) rejected BALB/c (H-2d) cardiac allografts earlier than uninfected recipients (6.9 +/- 0.1 d compared with 8.1 +/- 0.6 d; P < 0.001). It has been hypothesized that MCMV epitopes crossreact with alloantigens and in this manner induce rejection. However, we also demonstrated that MCMV caused accelerated rejection in the reverse combination (C3H heart engrafted to BALB/c recipient; 7.2 +/- 0.3 and 9.4 +/- 0.4 d for infected and control animals, respectively; P < 0.001) and accelerated rejection of grafts of a third, unrelated haplotype (C57Bl/6; H-2b; 8.0 +/- 0.7 d compared with 10.1 +/- 0.6 for infected and control C3H recipients, respectively; P < 0.03). Ultraviolet (UV) inactivation of MCMV before administration to the graft recipient abrogated the ability to induce rapid rejection. Activated T lymphocytes were present in grafts from infected recipients 2 d before control recipients (P < 0.02) and, at the time of graft rejection, were almost exclusively CD8+ for both infected and control recipients. Thus, MCMV accelerated rejection appears not to result from crossreaction between MCMV epitopes and MHC products. The failure of UV-inactivated virus to accelerate rejection and the high proportion of CD8+ T cells recovered from all rejected grafts suggest that the class I pathway of antigen presentation may be important in the induction of early rejection.

Animals↗
PubMed1991

HLA class II (DR and DQ) antigen associations in idiopathic dilated cardiomyopathy. Validation study and meta-analysis of published HLA association studies.

We previously reported antigen frequency differences for HLA-DR4 and HLA-DRw6 between idiopathic dilated cardiomyopathy (IDC) patients and healthy controls in a pilot study. To confirm these findings, we undertook an independent study with a prospective hypothesis regarding the frequencies of DR4 and DRw6; typing for a second family of class II antigens (HLA-DQ) was included because of the proximity of the DQ loci to the DR loci and the strong linkage disequilibrium between some of the DR and DQ alleles. Comparing a new consecutive series of IDC patients (n = 41) and healthy blood bank controls (n = 53), we confirmed an increase of DR4 antigen frequency in patients (49% versus 21%, p less than 0.005). A trend toward decreased expression of DRw6 among patients was also noted (10% of patients versus 23% of controls). HLA-DQw4 was significantly elevated in patients compared with controls (27% versus 6%, p less than 0.005; relative risk, 6.1; etiologic fraction, 0.22). We identified the combined DR4-DQw4 haplotype in five of 41 Caucasian IDC patients (12%) and none of 53 controls (p less than 0.007). A comparison of specific antigen frequencies between the preliminary and validation studies did not reveal significant differences; therefore, the data from the two studies were examined in combination. For the combined studies, DR4 was elevated (51% versus 27% in controls, p less than 0.001), and DRw6 was decreased (9% versus 24% in controls, p less than 0.01). The relative risk for DR4 was 2.8, and the etiologic fraction was 0.33.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiomyopathy, Dilated↗
PubMed1990

Correlation between class II antigen (DR) expression and interleukin-2-induced lymphocyte proliferation during acute cardiac allograft rejection.

We have previously reported a correlation between biopsy-proven rejection and the presence of IL-2-responsive lymphocytes for biopsy specimens from human cardiac allografts. We thus hypothesized a relationship between tissue expression of HLA class II antigen (DR) and the outgrowth of IL-2-responsive lymphocytes. Employing immunofluorescence DR staining with a propidium iodide counterstain in consecutive specimens from 41 patients, we found two patterns of DR expression: DR expressed on the vascular endothelial surface (donor antigens) and/or on myocardial infiltrating cells (presumably recipient antigens). Specimens were categorized by histologic diagnosis as "baseline nonrejecting controls" that were obtained 7.5 +/- 0.4 (mean +/- SE) days posttransplantation, "nonrejecting" (obtained 59.9 +/- 5.8 days posttransplantation), "prerejecting" (obtained 47.7 +/- 6.3 days posttransplantation), and "rejecting" (obtained 101.3 +/- 10.1 days posttransplantation). Prerejecting specimens were histologically negative specimens obtained from patients a mean of 6.0 +/- 0.4 days before a biopsy-proven rejection episode. The percentage of specimens positive for interstitial DR staining were: less than 1% for controls, 30% for nonrejecting specimens, 68% for prerejecting, and 46% for rejecting. For vascular DR staining, 25% of control specimens were positive, 56% of nonrejecting, 74% of prerejecting, and 73% of rejecting specimens. Culture positivity was seen for 38% of controls, 35% of nonrejecting specimens, 79% of prerejecting, and 70% of rejecting. Vascular DR staining was higher than interstitial staining for all specimen categories. For the vascular pattern, the mean score was significantly higher for culture-positive specimens compared to culture negative (0.87 +/- 0.1 vs. 0.59 +/- 0.1; P less than 0.01). A similar relationship was not found for the interstitial pattern. Lymphocyte growth occurred in conjunction with vascular DR upregulation significantly more frequently than in conjunction with interstitial DR expression (65% vs. 35% of culture-positive specimens, P less than 0.0001). These findings suggest a relationship between DR expression, lymphocyte growth, and acute rejection. Vascular DR and interstitial DR patterns show several differences with respect to kinetics of expression and correlation with histology and culture, and thus may represent different processes.

Blood Vessels↗
PubMed1986

HLA-DR typing and lymphocyte subset evaluation in rheumatic heart disease: a search for immune response factors.

Several autoimmune diseases have been associated with increased frequencies of specific histocompatibility (HLA) antigens, particularly for the D (DR) locus, that may be linked to immune response genes. Rheumatic valvular heart disease (RHD) has been postulated to have autoimmune features, but HLA associations have not been established. We, therefore, performed HLA-DR typing in 33 consecutive patients with RHD and in 82 normal blood bank control subjects. We also evaluated the frequencies of lymphocyte subsets by means of monoclonal antibodies and immunofluorescence flow cytometry and made functional correlations for the natural killer cell (NKC) in patient subsets. The DR patterns in RHD were heterogeneous. However, significant differences were noted for DR4 and DR6. DR4 was present in 52% (17 of 33) of RHD patients vs 32% (26 of 82) of control subjects (p less than 0.05). DR6 was present in 6% (2 of 33) of patients vs 26% (21 of 82) of control subjects (p less than 0.02). The associated relative odds of DR4 was 2.3 and the etiologic fraction was 0.30. The relative odds of DR6 was 0.19 and the preventive fraction was 0.21. A distinct clinical profile was not associated with DR4 positivity or DR6 negativity. The frequency of lymphocyte subsets was not significantly changed except for OKT8. Median NKC numbers tended to be higher in RHD patients than in control subjects (p less than 0.05). In contrast, NKC functional activity tended to be lower in RHD; median lymphocyte to target cell (K562 line) ratio resulting in 50% killing (L/T 50) was 20.5 in RHD patients vs 11.5 in control subjects (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Quantitation of lymphocyte subsets by immunofluorescence flow cytometry in idiopathic dilated cardiomyopathy.

Idiopathic dilated cardiomyopathy (IDC) is a disease in which immune aberration has been postulated but not confirmed. The frequency of lymphocyte subsets was evaluated in 22 patients with IDC and in 22 blood bank control subjects, using monoclonal antibodies to cell surface markers to allow cell sorting by immunofluorescence flow cytometry. Eighteen patients with heart failure from other causes were also studied. Functional correlations were also made for the natural killer cell subset. Total T-cell frequency, determined with antihuman T (Hybritech), was similar in IDC and control groups: mean 73 +/- 12% in IDC patients and 70 +/- 9% in control subjects. B-cell frequency, determined with antihuman Ia (Hybritech), was also similar: 36 +/- 11% in IDC patients and 31 +/- 10% in control subjects. Helper T-cell frequency, identified by OKT4 (Ortho), averaged 47 +/- 11% in IDC and 44 +/- 8% in control subjects (difference not significant). Suppressor/cytotoxic T-cell frequency, established by OKT8, was the same: 28 +/- 8% in IDC and 30 +/- 7% in control subjects, although relative deficiency in suppressor functional activity has been reported in IDC. Helper to suppressor (OKT4/8) ratios, aberrant in many autoimmune diseases, did not differ significantly (IDC 1.9 +/- 0.8, control 1.5 +/- 0.6). Lymphocyte subsets and OKT4/8 ratio were also similar between IDC and heart failure patients. Natural killer cell frequencies, estimated using 2 antibodies (antihuman Leu-7 and Leu-11, Becton-Dickinson) were the same (9.3 +/- 4.9% in IDC patients, 9.0 +/- 4.5% in control subjects, Leu-7).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

HLA A, B and DR typing in idiopathic dilated cardiomyopathy: a search for immune response factors.

Several autoimmune diseases have been associated with increased frequencies of various histocompatibility antigen (HLA) types that may be linked to immune response genes. Idiopathic dilated cardiomyopathy (IDC) has been proposed as a disease with autoimmune features, but HLA associations have not been evaluated. We performed HLA typing in 37 consecutive patients with IDC. Patients with habitual alcoholism were excluded. Results showed that no single HLA type could account for most cases; IDC is a genetically heterogeneous disease. However, uneven distributions were noted for certain types. Haplotype frequency of B27 was 0.145 in patients vs 0.033 in 5,726 local control subjects (p less than 0.001). Other A and B frequencies (except A2) were evenly distributed. HLA DR typing also revealed differences. The DR4 locus was present in 54% (19 of 35) of patients, vs 32% (26 of 82) of blood bank control subjects (p less than 0.02). The associated relative risk of DR4 was 2.2 and the etiologic fraction 0.29. Sex, disease chronicity, functional class, ejection fraction and biopsy evidence of myocarditis did not distinguish DR4-positive from DR4-negative patients, but they were older (54 +/- 12 vs 42 +/- 14 years, p less than 0.02). Of note, 68% were positive for DR4 or B27, or both. HLA DR6Y was underrepresented; it was present in 9% (3 of 35) of patients, vs 26% (21 of 82) of control subjects (p less than 0.04). The relative risk of DR6Y was 0.27 and the preventive fraction 0.19. These associations will require independent confirmation. However, they suggest that genetically determined immune response factors associated with HLA loci may play a role in pathogenesis in certain patients with IDC.

ABO Blood-Group System↗
PubMed1982

Deficient natural killer cell activity in patients with idiopathic dilated cardiomyopathy.

Dilated (congestive) cardiomyopathy is a disease of uncertain aetiology in which viral and immune factors are postulated to be of importance. Natural killer cells mediate natural resistance to viral infections and certain tumours. To evaluate natural killer (NK) activity in patients with cardiomyopathy, circulating peripheral blood mononuclear cells were obtained from 16 patients, from 54 normal blood donors, and from 14 patients with heart failure due to other causes (primarily coronary disease). NK activity was assessed as a lymphocyte to target cell ratio causing 50% killing (L/T50). L/T50 in normals was 17.2 +/- 11.4. A normal L/T50 distribution was also noted in heart failure controls (L/T50 = 19.6 +/- 9.9) and 8/16 cardiomyopathy patients (L/T50 = 17.5 +/- 9.5). NK activity was deficient (L/T50 greater than or equal to 50) in 8/16 patients with cardiomyopathy but in only 2/54 normals (p less than 0.001) and 0/14 heart failure controls (p less than 0.01). Of the several clinical and laboratory variables examined, only the frequency of the HLA-A3 tissue type was associated with NK deficiency. NK deficiency is an independent disease marker in about 50% of patients with cardiomyopathy and should be evaluated for a possible role in its pathogenesis.

Adult↗