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HLA antigen in three types of glomerulonephritis
.:LIXICAL
IMMUNOLOGY
AND
IMMUNOPATHOLOGY
Antigen k.
H.
Clinique
NOEL,~
19 - 23 (1978)
10,
in Three Types of Glomerulonephritisl B. DESCAMPS, C. SUET, J.
N6pilrologique, Saint
P. HORS,
J. F.
JUNGERS, AND
J.
BACH,
M. BUS~ON,
DAUSSET
INSERM U 25. Hdpital Necker. 75015 Paris, Louis. INSERM I/ 93, 75010 Paris, Frmce
and Hripitul
Received July 5, 1977 HLA antigens were studied in 98 patients with glomerulonephritis. No significant differences in the frequency of HLA antigens from normal individuals were found in focal and segmental glomerulosclerosis. Conversely, in membranoproliferative glomerulonephritis with dense deposits, the frequency of HLA B7 was increased (44 vs 19% in 591 healthy controls) although not significantly. In glomerulonephritis with IgA mesangial deposits, BW35 was present in 48% of 29 patients compared to 18% in the control group (P < 0.0002. corrected P < 0.005). Furthermore, in the latter case, the risk of recurrence after renal transplantation was significantly higher when the donor was a related HLA identical or haploidentical than a cadaver (P < 0.01).
INTRODUCTION
Little information is available on HLA antigens in renal diseases. Pate1 et al. (l), Mickey et al. (2), and Jensen et al. (3) have reported an increase of the A2 antigen frequency in chronic glomerulonephritis (GN). We have studied the frequency of HLA antigens in three types of chronic GN by taking advantage of the GN classification made possible by light and electron microscopy and immunofluorescence. Ninety-eight patients with GN could thus be investigated presenting membranoproliferative GN (MPGN), GN with 1gA mesangial deposits, or focal and segmental glomerulosclerosis (FSGN). MATERIALS
AND METHODS
HLA typing was performed using the microlymphocytotoxicity test adapted from Terasaki’s technique (4) for 28 specificities (12 from the HLA A and 16 from the HLA B loci) in 98 patients who were all Caucasian. A normal Caucasian French population of 591 subjects was used as controls. The antigen frequencies in normal and diseased subjects were compared two by two. The x2 test was used for statistical comparison. The P values were corrected (PC) by multiplying them by 28, i.e., the number of HLA alleles tested. The relative risk (RR) to be diseased when bearing a given antigen was calculated following the Haldane formula, as proposed by Svejgaard (13). The diagnosis was based on findings using light and/or electron microscopy and immunofluorescence.
’ Presented at the First HLA and Disease Symposium, Paris, June 1976. 1 Reprint requests should be sent to L. H. Noel. M. D., Clinique Nephrologique. Hopital Necker. 75015 Paris, France.
INSERM
U 2”.
19 0090-1229/78/0101-0019$01.00/0 Copyright All rights
@ 1978 by Academic Press. Inc. of reproduction rn any form reserved
20
NOtiL
ET AL
Three groups of GN were considered: (i) Fifty-one patients had a MPGN. This group was divided into three subgroups: MPGN with subendothelial deposits (25 patients) (5, 6), lobular GN (10 patients) (7), and dense deposits GN (16 patients) (8). (ii) Eighteen patients had nephrotic syndrome and FSGN (9, IO). (iii) Primary GN with mesangial deposits of IgA or Berger’s disease was studied in 29 patients (11, 12). All patients had reached the terminal stage of uremia, and $4 of them had received a kidney transplant. In the case of the transplanted patients, the kidney graft donor was a relative in 37 cases and a cadaver in 47 cases. The frequency tioned above and !i) MPGN. No tested was found
RESULTS of the HLA antigens among the various groups of patients menin the normal French population is given in Table 1. significant increase or decrease in any of the HLA specificities in patients with subendothelial deposits or in those with lobular
HLA Subendothelial deposits GNU (25 cases) LOCUS A Al A2 A3 A9 A10 All A28 A29 W19.2O AW32 .4w33 LOCUS B5 Bl B8 B12 B13 B14 B18 B21 BW15 BW17 BW21 BW22 SW35 BW37 BW38 BW40
28 36 28 24 12 4 8 8 12 0
Lobular GNU (10 cases)
TABLE ! B ASTICENS
A ~SD
deposits GN” (16 cases)
FREQULNCIES
Dense
30 50 10 20 0 0 20 20 30 0 0
25 44 25 31
10 10 40 40 0
0 44**
MPGN (51 cases)
19 6 13 19 0 0
FSGN (18 cases)
28 42 24 26 8 8 10 10 16
16 55 28 28 II 22 II 6 0
0
0
14 32* 28 28
22 11 11 33 6 0 0 16 16 0 0
Berger’s disease (29 cases)
Healthy controls (591)
17 62 31 14 10 14
14 0 0
23 44 26 24 12 12 6 11 10 5 1
14 10 10 31
13 19 17 29
B 24 32 24 12 8 4 12 0 12 8 4 4 24 0 8
25 44 0
10 0 0 10 10 0 20 0 0 10
u Subendothelial deposits GN. MPGN. h AW19.2 = AW30 + AW31. x P < 0.05; PC. as. PC, P value XX P i 0.01: PC, ns. *M* P < 0.0002, PC < 0.005.
0 19 0 6 25 lobular
corrected
GN,
12 9 7 9 5 19 2
10 3
0 6 12 and
by multiplying
dense
48*“*
33 6 11 11 deposits
by the number
0 0 17
GN
are
of tested
the
alleles.
three
10 subgroups
of
HLA
ANTIGEN
IN
GLO~MERULONEPHRITIS
21
n patientswith densedepositsGN the frequencyof HLA B7was44YS19% in the normal population (P < 0.01, PC = ns) (ii) FSGN. HLA A2 was 55 vs 44% in the controls (PC = ns). (iii) Berg&s disease. The frequency of HLA BW35 was 48 vs 19% in the normai population (P < 0.0002, PC < 0.005). HLA A2 was 62 vs 44% in the controls (PC = ns). The calculated RR were 3.9 and 2.1 for the antigens BW35 and A2, respectively . The recurrence of GN was proven in 10 patients with MPGN, in 3 patients with FSGN, and in 9 patients with Berger’s disease. Details of the relationship between the donors and recipients of kidney grafts are given in Table 2. In the cases of Berger’s disease, the risk of recurrence is significantly higher in a related HLA identical or haploidentical kidney than in a kidney from a cadaver (P < 0.01) (Table 2). The HLA phenotypes of the nine patients having relapses of Berger’s disease and their donors are given in Table 3. Five out of nine patients were BW35. Of the five donors who were HLA identical sibs, only two were BW35. DISCUSSION
An abnormally high incidence of HLA A2 antigens has been reported in patients with chronic GN with terminal uremia (l-3). However, the term “glomerulonephritis’ ’ includes a large number of pathological entities, and such a diagnosis requires a precise pathologic description. We have chosen three types of GN which seem to be specific entities because of the high risk of recurrence of the initial lesion after renal transplantation (14-17). Patients with two of these three
TABLE RECURRENCE OF ‘THE GN OF THE DONOR-RECIPIENT
2
FOLLOWING THE RELATIONSHIP KIDSEY TRANSPLANT
Relationship HLA +a Subendothelial Lobular GN Dense deposits Total
deposits GN
MPGN”
GN
identical
0 0 1
disease”,c
sib -
Total +
4 2 2
1 1 3
1 5 1
related
2
Cadaver -
+
10 3 2
3 0 2
15
5
(ii)
* 7
(iv) FSGN
to recipient
5 (9
Berger’s
of donor
2
15 (iii)
3
2
8
(vi)
(v) 0
6 5 4
5
1
10
u Recurrence of the GN for the three types of donor-recipient relationships. * P values for the recurrence of MPGN vs Berger’s disease, in terms of the donor-recipient relationship. (i) vs (iv). P < 0.02: (iii) vs (v), P < 0.02: (iii) vs (vi), P not significant, (iv) vs (vi), P < 0.05: iv) vs (vi). P < 0.01. c The proportion of recurrence of Berger’s disease is 7110 when the grafted kidney was from a relative (identical of haplo identical). 517 when an identical kidney was grafted. and 2110 in the case of a cadaver donor (P < 0.01).
22
NOkL
ET AL.
TABLE 3 RECURREXCEOF BERGER’S DISEASE IN NISE GRAPIED PAIIESTS
--
HLA phenotypes* Relationship Identical sibs
Related non-HLA identical Unrelated
Recipient 2 1 29 2 3
3
Donor
2 10
7 7 35 7 35
21 15 -
2
‘9 3
5 12
21 -
2 3
3 32
7 40
15
2 10
7 7 35 7 35
21 15 -
1 29 2 3
10 2
28 3
5 12
35 40
2 2
9 3
35 35
27 15
-
3
2
1
-
(1The numbers indicate the HLA specificity. The nomenclature abbreviations (HLA-A, are omitted for simplification.
B, and W)
types of chronic GN. i.e., Berger’s disease and FSGN, were found to have a frequency of A2 antigen which was higher (although not significantly) than the control population (Table 1). In dense deposits GN a high frequency of B7 was noted. This fact, together with peculiar morphological aspects, persistent hypocomplementemia, and a high incidence of recurrence after transplantation, clearly suggests that dense deposits GN is a distinct entity (18). We have found in GN with IgA mesangial deposits a high frequency of BW35 antigen. This finding may be in keeping with the report of MacDonald (19) of a high incidence of BW35 in the mesangial proliferative tissues, but no immunofluorescence studies were reported. In addition, Nyulassy et al. (20) have found that patients with GN without proven streptococcal infection (ASLO < 200, possibly viral GN) have an increased incidence of BW35. Thus, it was suggested that BW35 could be linked to a “virus susceptibility” gene. As GN with IgA mesangial deposits is often discovered after a sore throat, our finding of a high BW35 incidence in IgA Berger’s disease may support Nuylassy‘s hypothesis. One should note, however, that GN with mesangial deposits is often associated with high IgA levels in the serum and that IgA mesangial deposits frequently recur on transplants without previous viral infection. Thus, one might argue that BW35 is associated with an abnormality in IgA production or catabolism. Finally, the fact that the recurrence of Berger’s disease was significantly higher when the grafted kidney was haploidentical and/or identical with the recipient than in the case of an unrelated kidney (P < 0.01) also may be of great importance. Strong arguments (21) support the hypothesis that the gene coding for a high frequency of BW35 antigen is not itself involved, but rather that a gene in linkage disequilibrium with the B locus gene inside the major histocompatibility complex is involved. The present data suggest that the target (mesangial cells) must bear the same specific determinant as those of the recipient’s own kidney. It is interest-
HLA
ANTIGEN
IN
GLOMERULONEPHRITIS
23
ing to note that these preliminary results are in agreement with the experimental model described in mice by Zinkernagel (22) and others. REFERENCES 1. Patel, R., Mickey, M. R., and Terasaki, P. I., &it. Med. J. 2, 424, 1969. 2. Mickey, M. R., Kreisler, M., and Terasaki, P. I., In Histocompatibility Testing” [P. I. Terasaki, Ed.), p. 237, Munksgaard, Copenhagen, 1970. 3. Jensen, II., Hyder, L. P., Nielsen. L. S., Clausen, E., Jorgensen, F.; and Jorgensen, H. E.. Tisslte Atltigerzs 6, 368, 1975. 4. Mittal, K. K., Mickey, M. R., Singal, D. P., and Terasaki, P. I., Transplnrztarion 6, 913. 1968. 5. Cameron. J. S., Glasgow, E. F., Ogg, C. S.. and White, R. H. R.. Brir. Med. J. 4, 7, 1970. 6. Habib. R., Kleinknecht, G., Gubler, M. C., and Levy, M.. CIirl. NrpA&. 1, 194. 1973. 7. Mandalenakis, N., Mendoza, N., Pirani, C. L., and Pollak. V. E.. Medecirle 50, 319, 1971. 8. Berger, J., and Galle, P., Presse M&d. 71, 2351, 1963. 9. Cameron, .I. S., Ogg, C. S.. Turner, D. R., and Weller. R. O., 111 “Glomerulonephritis” (P. Kincaid-Smith, T. H. Mathew, and E. L. Becker. Eds.), Part 1, p. 249. New York, 1973. 10. Habib, R., Kidlley It7t. 4, 355, 1974. 11. Berger, .I.. Tmnsplanf. Proc. 4, 939, 1969. 12. Davies, D. R., Tiche, J. R., Jones, N. F., and Brown, G. W., J. C/in. Pat/m/. 26, 672. 1973. 13. SveJgaard, A.. Platz, P., Ryder, L. P., Nielsen, L. S., and Thomsen M., Tvar?sp/anr. Ru. 22, 3, 197s. 14. Hume. D. W., and Bryant. C. P., Truarlsylant. Proc. 4, 673. 1972. 15. Schtirch, W.. Leski. M.. and Hinglais, N., Vir-chows Arch. A. Pathol. Anar. 66, 355, 1972. 16. Berger, J., Yaneva, H., Nabarra, B., and Barbanel, C., k’idney Irlt. 7, 232. 1975. 17. Noel, L. H.. Berger, J., Descamps, B., Kreis, H., Hinglais, N., Nabarra. B.. and Crosnier, .I,. 111 “Abstracts of the Sixth International Congress of Nephrology,” Florence, 197.5, No. 1026. 18. Droz, D., Zanetti, M., Noel, L. H., and Leibowitch, J., Nephrorz 19, 1. 1977. 19. MacDonald, I. M., Dumble, L. J., and Kincaid-Smith, T. H., In “HLA and Disease” Vol. 58, p, 203, Inserm. Paris, 1976. 20. Nyulassy, S., But, M., Sasinka, M., Pavlovic, M.. Hirschova, V., Kaiserove, M., and Stefanovic. .I.. hl “HLA and Disease” Vol. 58, p. 207, Inserm. Paris, 1976. 2i. “HLA and Disease,” Vol. 58, Inserm, Paris, 1976. 22. Zinkernagel, R. M., and Doherty, P. C., Nrlrlrre (Lo/l&r?) 251, 547, 1974.
IMMUNOLOGY
AND
IMMUNOPATHOLOGY
Antigen k.
H.
Clinique
NOEL,~
19 - 23 (1978)
10,
in Three Types of Glomerulonephritisl B. DESCAMPS, C. SUET, J.
N6pilrologique, Saint
P. HORS,
J. F.
JUNGERS, AND
J.
BACH,
M. BUS~ON,
DAUSSET
INSERM U 25. Hdpital Necker. 75015 Paris, Louis. INSERM I/ 93, 75010 Paris, Frmce
and Hripitul
Received July 5, 1977 HLA antigens were studied in 98 patients with glomerulonephritis. No significant differences in the frequency of HLA antigens from normal individuals were found in focal and segmental glomerulosclerosis. Conversely, in membranoproliferative glomerulonephritis with dense deposits, the frequency of HLA B7 was increased (44 vs 19% in 591 healthy controls) although not significantly. In glomerulonephritis with IgA mesangial deposits, BW35 was present in 48% of 29 patients compared to 18% in the control group (P < 0.0002. corrected P < 0.005). Furthermore, in the latter case, the risk of recurrence after renal transplantation was significantly higher when the donor was a related HLA identical or haploidentical than a cadaver (P < 0.01).
INTRODUCTION
Little information is available on HLA antigens in renal diseases. Pate1 et al. (l), Mickey et al. (2), and Jensen et al. (3) have reported an increase of the A2 antigen frequency in chronic glomerulonephritis (GN). We have studied the frequency of HLA antigens in three types of chronic GN by taking advantage of the GN classification made possible by light and electron microscopy and immunofluorescence. Ninety-eight patients with GN could thus be investigated presenting membranoproliferative GN (MPGN), GN with 1gA mesangial deposits, or focal and segmental glomerulosclerosis (FSGN). MATERIALS
AND METHODS
HLA typing was performed using the microlymphocytotoxicity test adapted from Terasaki’s technique (4) for 28 specificities (12 from the HLA A and 16 from the HLA B loci) in 98 patients who were all Caucasian. A normal Caucasian French population of 591 subjects was used as controls. The antigen frequencies in normal and diseased subjects were compared two by two. The x2 test was used for statistical comparison. The P values were corrected (PC) by multiplying them by 28, i.e., the number of HLA alleles tested. The relative risk (RR) to be diseased when bearing a given antigen was calculated following the Haldane formula, as proposed by Svejgaard (13). The diagnosis was based on findings using light and/or electron microscopy and immunofluorescence.
’ Presented at the First HLA and Disease Symposium, Paris, June 1976. 1 Reprint requests should be sent to L. H. Noel. M. D., Clinique Nephrologique. Hopital Necker. 75015 Paris, France.
INSERM
U 2”.
19 0090-1229/78/0101-0019$01.00/0 Copyright All rights
@ 1978 by Academic Press. Inc. of reproduction rn any form reserved
20
NOtiL
ET AL
Three groups of GN were considered: (i) Fifty-one patients had a MPGN. This group was divided into three subgroups: MPGN with subendothelial deposits (25 patients) (5, 6), lobular GN (10 patients) (7), and dense deposits GN (16 patients) (8). (ii) Eighteen patients had nephrotic syndrome and FSGN (9, IO). (iii) Primary GN with mesangial deposits of IgA or Berger’s disease was studied in 29 patients (11, 12). All patients had reached the terminal stage of uremia, and $4 of them had received a kidney transplant. In the case of the transplanted patients, the kidney graft donor was a relative in 37 cases and a cadaver in 47 cases. The frequency tioned above and !i) MPGN. No tested was found
RESULTS of the HLA antigens among the various groups of patients menin the normal French population is given in Table 1. significant increase or decrease in any of the HLA specificities in patients with subendothelial deposits or in those with lobular
HLA Subendothelial deposits GNU (25 cases) LOCUS A Al A2 A3 A9 A10 All A28 A29 W19.2O AW32 .4w33 LOCUS B5 Bl B8 B12 B13 B14 B18 B21 BW15 BW17 BW21 BW22 SW35 BW37 BW38 BW40
28 36 28 24 12 4 8 8 12 0
Lobular GNU (10 cases)
TABLE ! B ASTICENS
A ~SD
deposits GN” (16 cases)
FREQULNCIES
Dense
30 50 10 20 0 0 20 20 30 0 0
25 44 25 31
10 10 40 40 0
0 44**
MPGN (51 cases)
19 6 13 19 0 0
FSGN (18 cases)
28 42 24 26 8 8 10 10 16
16 55 28 28 II 22 II 6 0
0
0
14 32* 28 28
22 11 11 33 6 0 0 16 16 0 0
Berger’s disease (29 cases)
Healthy controls (591)
17 62 31 14 10 14
14 0 0
23 44 26 24 12 12 6 11 10 5 1
14 10 10 31
13 19 17 29
B 24 32 24 12 8 4 12 0 12 8 4 4 24 0 8
25 44 0
10 0 0 10 10 0 20 0 0 10
u Subendothelial deposits GN. MPGN. h AW19.2 = AW30 + AW31. x P < 0.05; PC. as. PC, P value XX P i 0.01: PC, ns. *M* P < 0.0002, PC < 0.005.
0 19 0 6 25 lobular
corrected
GN,
12 9 7 9 5 19 2
10 3
0 6 12 and
by multiplying
dense
48*“*
33 6 11 11 deposits
by the number
0 0 17
GN
are
of tested
the
alleles.
three
10 subgroups
of
HLA
ANTIGEN
IN
GLO~MERULONEPHRITIS
21
n patientswith densedepositsGN the frequencyof HLA B7was44YS19% in the normal population (P < 0.01, PC = ns) (ii) FSGN. HLA A2 was 55 vs 44% in the controls (PC = ns). (iii) Berg&s disease. The frequency of HLA BW35 was 48 vs 19% in the normai population (P < 0.0002, PC < 0.005). HLA A2 was 62 vs 44% in the controls (PC = ns). The calculated RR were 3.9 and 2.1 for the antigens BW35 and A2, respectively . The recurrence of GN was proven in 10 patients with MPGN, in 3 patients with FSGN, and in 9 patients with Berger’s disease. Details of the relationship between the donors and recipients of kidney grafts are given in Table 2. In the cases of Berger’s disease, the risk of recurrence is significantly higher in a related HLA identical or haploidentical kidney than in a kidney from a cadaver (P < 0.01) (Table 2). The HLA phenotypes of the nine patients having relapses of Berger’s disease and their donors are given in Table 3. Five out of nine patients were BW35. Of the five donors who were HLA identical sibs, only two were BW35. DISCUSSION
An abnormally high incidence of HLA A2 antigens has been reported in patients with chronic GN with terminal uremia (l-3). However, the term “glomerulonephritis’ ’ includes a large number of pathological entities, and such a diagnosis requires a precise pathologic description. We have chosen three types of GN which seem to be specific entities because of the high risk of recurrence of the initial lesion after renal transplantation (14-17). Patients with two of these three
TABLE RECURRENCE OF ‘THE GN OF THE DONOR-RECIPIENT
2
FOLLOWING THE RELATIONSHIP KIDSEY TRANSPLANT
Relationship HLA +a Subendothelial Lobular GN Dense deposits Total
deposits GN
MPGN”
GN
identical
0 0 1
disease”,c
sib -
Total +
4 2 2
1 1 3
1 5 1
related
2
Cadaver -
+
10 3 2
3 0 2
15
5
(ii)
* 7
(iv) FSGN
to recipient
5 (9
Berger’s
of donor
2
15 (iii)
3
2
8
(vi)
(v) 0
6 5 4
5
1
10
u Recurrence of the GN for the three types of donor-recipient relationships. * P values for the recurrence of MPGN vs Berger’s disease, in terms of the donor-recipient relationship. (i) vs (iv). P < 0.02: (iii) vs (v), P < 0.02: (iii) vs (vi), P not significant, (iv) vs (vi), P < 0.05: iv) vs (vi). P < 0.01. c The proportion of recurrence of Berger’s disease is 7110 when the grafted kidney was from a relative (identical of haplo identical). 517 when an identical kidney was grafted. and 2110 in the case of a cadaver donor (P < 0.01).
22
NOkL
ET AL.
TABLE 3 RECURREXCEOF BERGER’S DISEASE IN NISE GRAPIED PAIIESTS
--
HLA phenotypes* Relationship Identical sibs
Related non-HLA identical Unrelated
Recipient 2 1 29 2 3
3
Donor
2 10
7 7 35 7 35
21 15 -
2
‘9 3
5 12
21 -
2 3
3 32
7 40
15
2 10
7 7 35 7 35
21 15 -
1 29 2 3
10 2
28 3
5 12
35 40
2 2
9 3
35 35
27 15
-
3
2
1
-
(1The numbers indicate the HLA specificity. The nomenclature abbreviations (HLA-A, are omitted for simplification.
B, and W)
types of chronic GN. i.e., Berger’s disease and FSGN, were found to have a frequency of A2 antigen which was higher (although not significantly) than the control population (Table 1). In dense deposits GN a high frequency of B7 was noted. This fact, together with peculiar morphological aspects, persistent hypocomplementemia, and a high incidence of recurrence after transplantation, clearly suggests that dense deposits GN is a distinct entity (18). We have found in GN with IgA mesangial deposits a high frequency of BW35 antigen. This finding may be in keeping with the report of MacDonald (19) of a high incidence of BW35 in the mesangial proliferative tissues, but no immunofluorescence studies were reported. In addition, Nyulassy et al. (20) have found that patients with GN without proven streptococcal infection (ASLO < 200, possibly viral GN) have an increased incidence of BW35. Thus, it was suggested that BW35 could be linked to a “virus susceptibility” gene. As GN with IgA mesangial deposits is often discovered after a sore throat, our finding of a high BW35 incidence in IgA Berger’s disease may support Nuylassy‘s hypothesis. One should note, however, that GN with mesangial deposits is often associated with high IgA levels in the serum and that IgA mesangial deposits frequently recur on transplants without previous viral infection. Thus, one might argue that BW35 is associated with an abnormality in IgA production or catabolism. Finally, the fact that the recurrence of Berger’s disease was significantly higher when the grafted kidney was haploidentical and/or identical with the recipient than in the case of an unrelated kidney (P < 0.01) also may be of great importance. Strong arguments (21) support the hypothesis that the gene coding for a high frequency of BW35 antigen is not itself involved, but rather that a gene in linkage disequilibrium with the B locus gene inside the major histocompatibility complex is involved. The present data suggest that the target (mesangial cells) must bear the same specific determinant as those of the recipient’s own kidney. It is interest-
HLA
ANTIGEN
IN
GLOMERULONEPHRITIS
23
ing to note that these preliminary results are in agreement with the experimental model described in mice by Zinkernagel (22) and others. REFERENCES 1. Patel, R., Mickey, M. R., and Terasaki, P. I., &it. Med. J. 2, 424, 1969. 2. Mickey, M. R., Kreisler, M., and Terasaki, P. I., In Histocompatibility Testing” [P. I. Terasaki, Ed.), p. 237, Munksgaard, Copenhagen, 1970. 3. Jensen, II., Hyder, L. P., Nielsen. L. S., Clausen, E., Jorgensen, F.; and Jorgensen, H. E.. Tisslte Atltigerzs 6, 368, 1975. 4. Mittal, K. K., Mickey, M. R., Singal, D. P., and Terasaki, P. I., Transplnrztarion 6, 913. 1968. 5. Cameron. J. S., Glasgow, E. F., Ogg, C. S.. and White, R. H. R.. Brir. Med. J. 4, 7, 1970. 6. Habib. R., Kleinknecht, G., Gubler, M. C., and Levy, M.. CIirl. NrpA&. 1, 194. 1973. 7. Mandalenakis, N., Mendoza, N., Pirani, C. L., and Pollak. V. E.. Medecirle 50, 319, 1971. 8. Berger, J., and Galle, P., Presse M&d. 71, 2351, 1963. 9. Cameron, .I. S., Ogg, C. S.. Turner, D. R., and Weller. R. O., 111 “Glomerulonephritis” (P. Kincaid-Smith, T. H. Mathew, and E. L. Becker. Eds.), Part 1, p. 249. New York, 1973. 10. Habib, R., Kidlley It7t. 4, 355, 1974. 11. Berger, .I.. Tmnsplanf. Proc. 4, 939, 1969. 12. Davies, D. R., Tiche, J. R., Jones, N. F., and Brown, G. W., J. C/in. Pat/m/. 26, 672. 1973. 13. SveJgaard, A.. Platz, P., Ryder, L. P., Nielsen, L. S., and Thomsen M., Tvar?sp/anr. Ru. 22, 3, 197s. 14. Hume. D. W., and Bryant. C. P., Truarlsylant. Proc. 4, 673. 1972. 15. Schtirch, W.. Leski. M.. and Hinglais, N., Vir-chows Arch. A. Pathol. Anar. 66, 355, 1972. 16. Berger, J., Yaneva, H., Nabarra, B., and Barbanel, C., k’idney Irlt. 7, 232. 1975. 17. Noel, L. H.. Berger, J., Descamps, B., Kreis, H., Hinglais, N., Nabarra. B.. and Crosnier, .I,. 111 “Abstracts of the Sixth International Congress of Nephrology,” Florence, 197.5, No. 1026. 18. Droz, D., Zanetti, M., Noel, L. H., and Leibowitch, J., Nephrorz 19, 1. 1977. 19. MacDonald, I. M., Dumble, L. J., and Kincaid-Smith, T. H., In “HLA and Disease” Vol. 58, p, 203, Inserm. Paris, 1976. 20. Nyulassy, S., But, M., Sasinka, M., Pavlovic, M.. Hirschova, V., Kaiserove, M., and Stefanovic. .I.. hl “HLA and Disease” Vol. 58, p. 207, Inserm. Paris, 1976. 2i. “HLA and Disease,” Vol. 58, Inserm, Paris, 1976. 22. Zinkernagel, R. M., and Doherty, P. C., Nrlrlrre (Lo/l&r?) 251, 547, 1974.