Tissue Antigens (1978)’11,129-131 Published by Munksgaard, Copenhagen, Denmark No part may be reproduced by any process without written permission from the authorb)
HL-A Antigens of Patients with Wegener’s Granulomatosis C. Vaughn Strimlan, Howard F. Taswell, Friedrich Kueppers, Richard A. DeRemee, and Thomas J. McDonald Mayo Clinic and Mayo Foundation, Rochester, Minnesota, U.S.A. The frequency of HL-A antigens was determined in 31 patients with biopsy-confirmed Wegener’s granulomatosis and compared with their frequency in healthy Caucasian control population. There was no significant difference between the two groups for any of the 24 HL-A antigens tested. Received for publication 4 July 1977, accepted 2%August 1977
Wegener’s granulomatosis is characterized suppressive therapy with cyclophosphaby necrotizing granulomatous vasculitis mide further support the concept that this involving the upper or lower respiratory is an immunologically mediated disease tract and focal necrotizing glomerulitis (Wolff et al. 1974). Since evidence exists that HL-A antigens (Godman & Churg 1954). It also may occur in a limited or localized form with- are related to the immune response, posout renal involvement (Carrington & sibly because of a close linkage with Liebow 1966).The disease is believed to be immune response genes, we determined the immunologically mediated, although the HL-A antigens in a series of unrelated exact cause is unknown. Several recent patients who had Wegener’s granulomatosis studies have shown that various immu- and in a healthy Caucasian control populanologic abnormalities occur in this tion. disorder. Patients with Wegener’s granuloMaterial and Methods rnatosis may have elevated levels of serum IgA or of smooth muscle autoantibodies Thirty-one patients with Wegener’s granu(Shillitoe et al. 1974). Serum IgE levels lomatosis were selected from available may be significantly elevated (Conn et al. patients with Wegener’s granulomatosis 1976). An immune complex-mediated being followed at the Mayo Clinic. All 31 glomerulonephritis can occur in these patients had biopsy-confirmed lesions patients (Fauci & Wolff 1973). Long-term involving the uppe‘r respiratory tract, the favorable clinical responses to immuno- lower respiratory tract, or the kidneys. Of
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Table 1 HL-A antigen frequency in 31 patients with Wegener ‘s granulomatosis Healthy controls
HL-A antigen
No. tested
A1 A2 A3 A9 A10 A1 1 A28 A29 AW33
701 701 701 701 701 607 390 237 593
B5 B7 B8 B12 B13 B14 B18 B27 BW15 BW16 BW17 BW21 BW22 BW35 BW40
.
701 70 1 701 701
701 701 549 600 567 550 567 102 584 583 701
Wegener’s granulomatosis % pos.
Locus A 29.5 50.8 24.4 17.8 9.1 10.4 3.8 6.3 11.8 Locus B 10.4 22.3 24.1 25.7 3.7 4.9 8.4 8.7 11.5 3.6 6.7 2.9 2.7 12.2 16.3
the 31 patients, 15 had two or three systems involved: six had upper and lower respiratory tract involvement as well as kidney involvement, six had upper and lower respiratory tract involvement, one had lower respiratory tract and kidney involvement, and two had upper respiratory tract and kidney involvement. Sixteen of the 31 patients had one system involved: 12 the upper and four the lower respiratory tract. A11 31 patients (19 men and 12 women) were Caucasians. Their mean age was 49.4 years, with a range of 21 to 79 years. The duration of disease ranged from 40 to 240 months, with a mean of 53.5 months.
No. pos.
% pos.
13 13 12 6 3 6 0 4 1
41.9 41.9 38.7 19.4 9.7 19.4
3 10 9 8 1
9.7 32.3 29.0 25.8 3.2 0 9.7 6.5 9.7 3.2 16.1 0 0 22.6 12.9
0
3 2 3
1 5 0 0 7
4
0
12.9 3.2
HL-A typing of the lymphocytes was performed using the microdroplet lymphocyte cytotoxicity assay (Mittal e t al. 1968). A total of 24 HL-A antigens (A and B loci) were tested using both NIH supplied and locally acquired sera (Table 1). Statistical evaluation of the results was made using x2 analysis and Fisher’s exact test.
Results The results are shown in Table 1. The frequency of HL-A antigens occurring in the patient group was similar t o the frequencies observed in the control population of healthy Caucasian blood donors. Statistical
HL-A ANTIGENS OF PATIENTS WITH WEGENER’S GRANULOMATOSIS
analysis did not show any significant difference between the two groups.
Discussion All of the patients in our series had biopsyconfirmed Wegener’s granulomatosis, either of the generalized or localized form. There were no correlations between specific HL-A antigens and site of anatomic involvement, and n o significant difference in the HL-A antigen frequencies comparing the patient series and the control population. Based on a relatively small number of patients, no HL-A antigen showed a strong association with Wegener’s granulomatosis. Although our results d o not disprove the importance of immunologic mechanisms in Wegener’s granulomatosis, we may assume that HL-A antigens are not major predisposing factors.
Acknowledgments We thank Dr. L. R. Elveback for her statistical analysis of the data and Mrs. D. Clare, Miss L. Kraling, and Mrs. A. Tietje for their technical assistance.
131
References Carrington. C. B. & Liebow, A. A. (1966) Limited forms of angiitis and granulomatosis of Wegener’s type. Amer. J . Med. 41,497-527. Conn, D. L., Gleich, G. J., DeRemee, R. A. & McDonald, T. J. (1976) Raised serum immunoglobulin E in Wegener’s granulomatosk. Ann. rheum. Dk. 35, 377-380. Fauci, A. S. & Wolff, S. M. (1973) Wegener’s granulomatosis: studies in eighteen patients and a review of the literature. Medicine, Baltimore 5 2 : 535-561. Godman, G. C. & Churg, J. (1954) Wegener’s granulomatosis: pathology and review of the literature. Arch. Path. 58, 533-553. Mittal, K. K., Mickey, M. R., Singal, D. P. & Terasaki, P. I. (1968) Serotyping for homotransplantation. XVIII. Refinement of microdroplet lymphocyte cytotoxicity test. Transplantation 6,913-927. Shillitoe, E. J., Lehner, T., Lessof, M. H. & Harrison, D. F. N. (1974) Immunological features of Wegener’s granulomatosis. Lancet 1,281-284.
Wolff, S . M., Fauci, A. S., Horn, R. G. & Dale, D. C. (1974) Wegener’s granulomatosis. Ann. intern. Med. 81,513-525. Address: Dr. Howard F. Taswell
Blood Bank and Transfusion Service Mayo Clinic Rochester, Minnesota 55901 USA.
HL-A Antigens of Patients with Wegener’s Granulomatosis C. Vaughn Strimlan, Howard F. Taswell, Friedrich Kueppers, Richard A. DeRemee, and Thomas J. McDonald Mayo Clinic and Mayo Foundation, Rochester, Minnesota, U.S.A. The frequency of HL-A antigens was determined in 31 patients with biopsy-confirmed Wegener’s granulomatosis and compared with their frequency in healthy Caucasian control population. There was no significant difference between the two groups for any of the 24 HL-A antigens tested. Received for publication 4 July 1977, accepted 2%August 1977
Wegener’s granulomatosis is characterized suppressive therapy with cyclophosphaby necrotizing granulomatous vasculitis mide further support the concept that this involving the upper or lower respiratory is an immunologically mediated disease tract and focal necrotizing glomerulitis (Wolff et al. 1974). Since evidence exists that HL-A antigens (Godman & Churg 1954). It also may occur in a limited or localized form with- are related to the immune response, posout renal involvement (Carrington & sibly because of a close linkage with Liebow 1966).The disease is believed to be immune response genes, we determined the immunologically mediated, although the HL-A antigens in a series of unrelated exact cause is unknown. Several recent patients who had Wegener’s granulomatosis studies have shown that various immu- and in a healthy Caucasian control populanologic abnormalities occur in this tion. disorder. Patients with Wegener’s granuloMaterial and Methods rnatosis may have elevated levels of serum IgA or of smooth muscle autoantibodies Thirty-one patients with Wegener’s granu(Shillitoe et al. 1974). Serum IgE levels lomatosis were selected from available may be significantly elevated (Conn et al. patients with Wegener’s granulomatosis 1976). An immune complex-mediated being followed at the Mayo Clinic. All 31 glomerulonephritis can occur in these patients had biopsy-confirmed lesions patients (Fauci & Wolff 1973). Long-term involving the uppe‘r respiratory tract, the favorable clinical responses to immuno- lower respiratory tract, or the kidneys. Of
VAUGHN STRIMLAN ET AL.
130
Table 1 HL-A antigen frequency in 31 patients with Wegener ‘s granulomatosis Healthy controls
HL-A antigen
No. tested
A1 A2 A3 A9 A10 A1 1 A28 A29 AW33
701 701 701 701 701 607 390 237 593
B5 B7 B8 B12 B13 B14 B18 B27 BW15 BW16 BW17 BW21 BW22 BW35 BW40
.
701 70 1 701 701
701 701 549 600 567 550 567 102 584 583 701
Wegener’s granulomatosis % pos.
Locus A 29.5 50.8 24.4 17.8 9.1 10.4 3.8 6.3 11.8 Locus B 10.4 22.3 24.1 25.7 3.7 4.9 8.4 8.7 11.5 3.6 6.7 2.9 2.7 12.2 16.3
the 31 patients, 15 had two or three systems involved: six had upper and lower respiratory tract involvement as well as kidney involvement, six had upper and lower respiratory tract involvement, one had lower respiratory tract and kidney involvement, and two had upper respiratory tract and kidney involvement. Sixteen of the 31 patients had one system involved: 12 the upper and four the lower respiratory tract. A11 31 patients (19 men and 12 women) were Caucasians. Their mean age was 49.4 years, with a range of 21 to 79 years. The duration of disease ranged from 40 to 240 months, with a mean of 53.5 months.
No. pos.
% pos.
13 13 12 6 3 6 0 4 1
41.9 41.9 38.7 19.4 9.7 19.4
3 10 9 8 1
9.7 32.3 29.0 25.8 3.2 0 9.7 6.5 9.7 3.2 16.1 0 0 22.6 12.9
0
3 2 3
1 5 0 0 7
4
0
12.9 3.2
HL-A typing of the lymphocytes was performed using the microdroplet lymphocyte cytotoxicity assay (Mittal e t al. 1968). A total of 24 HL-A antigens (A and B loci) were tested using both NIH supplied and locally acquired sera (Table 1). Statistical evaluation of the results was made using x2 analysis and Fisher’s exact test.
Results The results are shown in Table 1. The frequency of HL-A antigens occurring in the patient group was similar t o the frequencies observed in the control population of healthy Caucasian blood donors. Statistical
HL-A ANTIGENS OF PATIENTS WITH WEGENER’S GRANULOMATOSIS
analysis did not show any significant difference between the two groups.
Discussion All of the patients in our series had biopsyconfirmed Wegener’s granulomatosis, either of the generalized or localized form. There were no correlations between specific HL-A antigens and site of anatomic involvement, and n o significant difference in the HL-A antigen frequencies comparing the patient series and the control population. Based on a relatively small number of patients, no HL-A antigen showed a strong association with Wegener’s granulomatosis. Although our results d o not disprove the importance of immunologic mechanisms in Wegener’s granulomatosis, we may assume that HL-A antigens are not major predisposing factors.
Acknowledgments We thank Dr. L. R. Elveback for her statistical analysis of the data and Mrs. D. Clare, Miss L. Kraling, and Mrs. A. Tietje for their technical assistance.
131
References Carrington. C. B. & Liebow, A. A. (1966) Limited forms of angiitis and granulomatosis of Wegener’s type. Amer. J . Med. 41,497-527. Conn, D. L., Gleich, G. J., DeRemee, R. A. & McDonald, T. J. (1976) Raised serum immunoglobulin E in Wegener’s granulomatosk. Ann. rheum. Dk. 35, 377-380. Fauci, A. S. & Wolff, S. M. (1973) Wegener’s granulomatosis: studies in eighteen patients and a review of the literature. Medicine, Baltimore 5 2 : 535-561. Godman, G. C. & Churg, J. (1954) Wegener’s granulomatosis: pathology and review of the literature. Arch. Path. 58, 533-553. Mittal, K. K., Mickey, M. R., Singal, D. P. & Terasaki, P. I. (1968) Serotyping for homotransplantation. XVIII. Refinement of microdroplet lymphocyte cytotoxicity test. Transplantation 6,913-927. Shillitoe, E. J., Lehner, T., Lessof, M. H. & Harrison, D. F. N. (1974) Immunological features of Wegener’s granulomatosis. Lancet 1,281-284.
Wolff, S . M., Fauci, A. S., Horn, R. G. & Dale, D. C. (1974) Wegener’s granulomatosis. Ann. intern. Med. 81,513-525. Address: Dr. Howard F. Taswell
Blood Bank and Transfusion Service Mayo Clinic Rochester, Minnesota 55901 USA.
