Sabouraudia (1979), 17, 261-264
ASSOCIATION OF ABO BLOOD G R O U P A N D O U T C O M E OF COCCIDIOIDAL INFECTION*STANLEY C. DERESINSKI, DEMOSTHENES PAPPAGIANISAND DAVID A. STEVENS**
Di~'ision of Infectious Diseases, Department of Medicine, University of South Florida Medical School, Tampa, Florida; Department of Medical Microbiology, University of California Medical School, Davis, California; Division of Infectious Diseases, Departments of Medicine, Santa Clara Valley Medical Center and Stanford University, San Jose and Stanford, California, U.S.A.
Dissemination of infection with Coccidioides immitis from its p r i m a r y site of implantation in the lung occurs with an estinated frequency of 1.0 °/o in adult white males (15). The hypothesis that hereditary factors determine predisposition to dissemination of infection with C. immitis is primarily based on epidemiologic data reported four decades ago (4). T h a t work suggests that the frequency of such dissemination is greater in certain dark-skinned than in light-skinned races. T h e reasons for such differences are completely u n k n o w n . Although Landau et al. (8) could not demonstrate blood group activity in autoclaved culture filtrates or powdered (autoclaved) mycelia of C. immitis, Gale et al. reported that culture filtrates contain blood group A activity (3). These findings led us to examine the possible role of ABO blood groups in the outcome of coccidioidal infection. MATERIALS AND METHODS Serum obtained from patients with active coccidioidal infection was tested for isoagglutinins A and B by a standard technique (13). Most of these sera were submitted by various physicians in endemic areas in California for complement fixing antibody (CFA) titration against coccidioidin, performed as previously described (16). We attempted to obtain sufficient n u m b e r s of sera from patients with pulmonary and with disseminated disease to enable comparisons. Allele frequencies were calculated using the H a r d y - W e i n b e r g relationship (6). T h e data were evaluated statistically by the Chi Square Test with Yates C o n t i n u i t y Correction. T h e usual definition of statistical significance of p < 0 " 0 5 was made more stringent by correction consisting of dividing 0-05 by 4, the n u m b e r of variables measured, so that only values of p < 0-01 would be considered statistically significant (5). *Supported in part by the John A. Harttord Foundation and U.S. Army Medical Research and DevelopmentCommand under Research Contract No. DADA 17-69-C-9061. **Address correspondence to Dr. D. A. Stevens, Department of Medicine, Santa Clara Valley Medical Center, 751 South Bascom Avenue, San Jose, California 95128, U.S.A. 261
Downloaded from http://sabouraudia.oxfordjournals.org/ at Yale University on July 6, 2015
Disseminationof fungal infection due to Coccidioidesimmitis has been previously shown to be related to hereditary factors. Two associations reported to date are race (e.g., Filipino and black ancestry) and HLA histocompatibility type (HLA-A9). In the present study of 105 patients a significantassociationof blood group B and disseminationis demonstrated. C. immitis is known to possess antigens with blood group A activity. Previous epidemiologicstudies have also shown HLA-A9 and blood group B are both more common in persons of black and Filipinoancestry. Further studies are needed to define whether these are independent variables, and may definesubgroups at particularly high risk followingcoccidioidalinfection.
262
DERESINSKI E T AL. RESULTS
E x a m i n a t i o n of blood group frequencies in patients with the various forms of the disease (Table 1 ) revealed only one significant comparison. Individuals of blood group B were more than twice as likely to have disseminated infection than infection confined t o the- lungs- (p < 0.001 ). D a t a ~from extensiv:e studies, of A B O blood groups in healthy donors are presented in the table for comparison (9). TABLE I.--BLooD GROUPS IN PATIENTS AND SUBJECTS
ABO Blood group 0
A
B
AB
Total
3 (0.07) 1 (0.07) 4 (O.O7)
3 (0.07) 1 (0-07) 4 (O.O7)
43 14 57
(0.32) (0.29) (0.31) (0-32)
7 (0.17) 1 (0-14) 8 (0.17) 12 (0.11)
1 (0.02) 0 1 (0.02) 5 (0.05)
41 7 48 105
{0-40) {0.22) (0.27)
(0.10) (0.27) (0-20)
(0-04) (0.06) (0.04)
16038 382 6722
Coceidioidomycosis patients
1. Pulmonary a. Non-Cavitary b. Cavitary c. Total
23 (0-53)a 7 (0-50) 3O (0-53)
14 (0.33) 5 (0.36) 19 (0.33)
20 4 24 54
13 2 15 34
2. Disseminated
a. Non-Meningeal b. Meningeal c. Total Total patients
(0-49) (0-57) (0.50) (0.51)
Healthy subjectsb
California white blood donors Filipino-Americans American blacks
(0.46) (0-45) (0.49)
~Number (frequency) UReference 9 C F A titers were examined within categories of disease in relation to A B O blood groups. T h e m e d i a n titers in patients with disease limited to the thoracic cavity were 1:4 in patients with blood groups A, B and AB and 1:8 in patients with blood group O. I n patients with disseminated infection, the m e d i a n titers for those of blood group A, B and AB were 1:16 and were 1:32 in those of blood group O. These differences within groups classified by extent of disease were not significant. DISCUSSION A n increased frequency of infections with certain g r a m - n e g a t i v e b a c t e r i a has been noted in patients with blood group B (2, 12, 17). M a n y of the organisms involved in these infections possess antigens that cross-react with blood group B, however (10, 18). T h e excess representation of the B blood group p h e n o t y p e (and presumably genotype) in patients with disseminated coccidioidomycosis is consistent with the hypothesis that h e r e d i t a r y factors are i m p o r t a n t in the i m m u n e response to this infection. T h e finding, by Scheer et al., of a disproportionately increased frequency of the H L A - A 9 histocompatibility antigen p h e n o t y p e in patients with disseminated coccidioidomycosis (14), is also consistent with this hypothesis. T h e frequency of dissemination of coccidioidomycosis in Filipinos and blacks has been estimated at 175 and 10 times that of whites (4). T h e frequency of the blood
Downloaded from http://sabouraudia.oxfordjournals.org/ at Yale University on July 6, 2015
Category
BLOOD GROUP AND COCCIDIOIDOMYCOSIS
263
ABSTRACTO Se ha demostrado que la diseminacion de la infeccion de hongos que son el resultado de Coccidioides immitis se relaciona a factores hereditarios. Dos associaciones que se han reportado son raza (por ejemplo: desendencia Filipina y Negra) e histocompatibilidad tipo HLA (HLA-A9). En este estudio de 105 pacientes una associacion de tipo sanguieno tipo B (p
ASSOCIATION OF ABO BLOOD G R O U P A N D O U T C O M E OF COCCIDIOIDAL INFECTION*STANLEY C. DERESINSKI, DEMOSTHENES PAPPAGIANISAND DAVID A. STEVENS**
Di~'ision of Infectious Diseases, Department of Medicine, University of South Florida Medical School, Tampa, Florida; Department of Medical Microbiology, University of California Medical School, Davis, California; Division of Infectious Diseases, Departments of Medicine, Santa Clara Valley Medical Center and Stanford University, San Jose and Stanford, California, U.S.A.
Dissemination of infection with Coccidioides immitis from its p r i m a r y site of implantation in the lung occurs with an estinated frequency of 1.0 °/o in adult white males (15). The hypothesis that hereditary factors determine predisposition to dissemination of infection with C. immitis is primarily based on epidemiologic data reported four decades ago (4). T h a t work suggests that the frequency of such dissemination is greater in certain dark-skinned than in light-skinned races. T h e reasons for such differences are completely u n k n o w n . Although Landau et al. (8) could not demonstrate blood group activity in autoclaved culture filtrates or powdered (autoclaved) mycelia of C. immitis, Gale et al. reported that culture filtrates contain blood group A activity (3). These findings led us to examine the possible role of ABO blood groups in the outcome of coccidioidal infection. MATERIALS AND METHODS Serum obtained from patients with active coccidioidal infection was tested for isoagglutinins A and B by a standard technique (13). Most of these sera were submitted by various physicians in endemic areas in California for complement fixing antibody (CFA) titration against coccidioidin, performed as previously described (16). We attempted to obtain sufficient n u m b e r s of sera from patients with pulmonary and with disseminated disease to enable comparisons. Allele frequencies were calculated using the H a r d y - W e i n b e r g relationship (6). T h e data were evaluated statistically by the Chi Square Test with Yates C o n t i n u i t y Correction. T h e usual definition of statistical significance of p < 0 " 0 5 was made more stringent by correction consisting of dividing 0-05 by 4, the n u m b e r of variables measured, so that only values of p < 0-01 would be considered statistically significant (5). *Supported in part by the John A. Harttord Foundation and U.S. Army Medical Research and DevelopmentCommand under Research Contract No. DADA 17-69-C-9061. **Address correspondence to Dr. D. A. Stevens, Department of Medicine, Santa Clara Valley Medical Center, 751 South Bascom Avenue, San Jose, California 95128, U.S.A. 261
Downloaded from http://sabouraudia.oxfordjournals.org/ at Yale University on July 6, 2015
Disseminationof fungal infection due to Coccidioidesimmitis has been previously shown to be related to hereditary factors. Two associations reported to date are race (e.g., Filipino and black ancestry) and HLA histocompatibility type (HLA-A9). In the present study of 105 patients a significantassociationof blood group B and disseminationis demonstrated. C. immitis is known to possess antigens with blood group A activity. Previous epidemiologicstudies have also shown HLA-A9 and blood group B are both more common in persons of black and Filipinoancestry. Further studies are needed to define whether these are independent variables, and may definesubgroups at particularly high risk followingcoccidioidalinfection.
262
DERESINSKI E T AL. RESULTS
E x a m i n a t i o n of blood group frequencies in patients with the various forms of the disease (Table 1 ) revealed only one significant comparison. Individuals of blood group B were more than twice as likely to have disseminated infection than infection confined t o the- lungs- (p < 0.001 ). D a t a ~from extensiv:e studies, of A B O blood groups in healthy donors are presented in the table for comparison (9). TABLE I.--BLooD GROUPS IN PATIENTS AND SUBJECTS
ABO Blood group 0
A
B
AB
Total
3 (0.07) 1 (0.07) 4 (O.O7)
3 (0.07) 1 (0-07) 4 (O.O7)
43 14 57
(0.32) (0.29) (0.31) (0-32)
7 (0.17) 1 (0-14) 8 (0.17) 12 (0.11)
1 (0.02) 0 1 (0.02) 5 (0.05)
41 7 48 105
{0-40) {0.22) (0.27)
(0.10) (0.27) (0-20)
(0-04) (0.06) (0.04)
16038 382 6722
Coceidioidomycosis patients
1. Pulmonary a. Non-Cavitary b. Cavitary c. Total
23 (0-53)a 7 (0-50) 3O (0-53)
14 (0.33) 5 (0.36) 19 (0.33)
20 4 24 54
13 2 15 34
2. Disseminated
a. Non-Meningeal b. Meningeal c. Total Total patients
(0-49) (0-57) (0.50) (0.51)
Healthy subjectsb
California white blood donors Filipino-Americans American blacks
(0.46) (0-45) (0.49)
~Number (frequency) UReference 9 C F A titers were examined within categories of disease in relation to A B O blood groups. T h e m e d i a n titers in patients with disease limited to the thoracic cavity were 1:4 in patients with blood groups A, B and AB and 1:8 in patients with blood group O. I n patients with disseminated infection, the m e d i a n titers for those of blood group A, B and AB were 1:16 and were 1:32 in those of blood group O. These differences within groups classified by extent of disease were not significant. DISCUSSION A n increased frequency of infections with certain g r a m - n e g a t i v e b a c t e r i a has been noted in patients with blood group B (2, 12, 17). M a n y of the organisms involved in these infections possess antigens that cross-react with blood group B, however (10, 18). T h e excess representation of the B blood group p h e n o t y p e (and presumably genotype) in patients with disseminated coccidioidomycosis is consistent with the hypothesis that h e r e d i t a r y factors are i m p o r t a n t in the i m m u n e response to this infection. T h e finding, by Scheer et al., of a disproportionately increased frequency of the H L A - A 9 histocompatibility antigen p h e n o t y p e in patients with disseminated coccidioidomycosis (14), is also consistent with this hypothesis. T h e frequency of dissemination of coccidioidomycosis in Filipinos and blacks has been estimated at 175 and 10 times that of whites (4). T h e frequency of the blood
Downloaded from http://sabouraudia.oxfordjournals.org/ at Yale University on July 6, 2015
Category
BLOOD GROUP AND COCCIDIOIDOMYCOSIS
263
ABSTRACTO Se ha demostrado que la diseminacion de la infeccion de hongos que son el resultado de Coccidioides immitis se relaciona a factores hereditarios. Dos associaciones que se han reportado son raza (por ejemplo: desendencia Filipina y Negra) e histocompatibilidad tipo HLA (HLA-A9). En este estudio de 105 pacientes una associacion de tipo sanguieno tipo B (p
