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RACIAL DIFFERENCE IN THE PREVALENCE OF IgA-ASSOCIATED NEPHROPATHIES
522 RACIAL DISTRIBUTION OF SEVERAL POPULATIONS WITH
of diagnosis are in the experimental phase. In this case culture of half the biopsy sample avoided a late diagnosis and the stress and risk associated with a prostaglandin termination. We recommend this dual approach to first-trimester diagnosis of argininosuccinicaciduria and citrullinaemia, and it may well prove useful for other metabolic diseases. Paediatric Research
Unit,
Guy’s Hospital Medical School, London SE1 9RT
IgA-ASSOCIATED
DISEASES
C. M. VIMAL A. H. FENSOM
Cytogenetics Unit, St Mary’s Hospital Medical School, London W2
D. HEATON
Department of Obstetrics and Gynaecology, University College Hospital, London WC1
Faculty
R. H. T. WARD
of Clinical Sciences,
School of Medicine, University College London
P. GARROD
Galton Laboratory, Department of Genetics and Biometry, University College London
R.
J. A. PENKETH
Young EP, Patrick AD. First trimester diagnosis of metabolic diseases Prenatal Diagnosis Group News! 1983; 7 (Dec): 4-5. 2. Fensom AH, Jackson M, Sanguinetti N, et al. The use of chorionic villi for early prenatal diagnosis of metabolic disorders. J Med Genet 1984; 21: 142 (abstr). 3 Simoni G, Brambati B, Danesino C, et al Diagnostic application of first trimester trophoblast sampling in 100 pregnancies. Hum Genet 1984; 66: 252-59. 4. Tedesco TA, Mellman WJ. Argmmosuccinate synthetase activity and citrulline 1
*Percentages in parentheses. tlncludes Children’s Hospital for this period but excludes biopsies of transplanted kidneys.
metabolism in cells cultured from citrullinemic subjects. Proc Natl Acad Sci USA 1967; 57: 829-39 5. Fensom AH, Benson PF, Baker JE, Mutton DE Prenatal diagnosis of argininosuccinic aciduria: Effect of mycoplasma contamination on the indirect assay for argminosuccinate lyase. Am J Hum Genet 1980; 32: 761-63 6 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent J Biol Chem 1951, 193: 265-75. 7. Ward RHT, Modell B, Petrou M, Karagozlu F, Douratsos E. Method of sampling
Notwithstanding these uncertainties, these observations regarding racial distribution support the notion that familial predisposition has an important role in the clinical expression of these common IgA-associated glomerular diseases.
chorionic villi in first trimester of pregnancy under guidance of real time ultrasound. Br Med J 1983; 286: 1542-44. 8. Heaton DE, Czepulkowski BH, Horwell DH, Coleman DV. Chromosome first trimester chorionic villus biopsies prepared by a maceration Prenatal Diagnosis 1984; 4: 279-87.
analysis of technique.
RACIAL DIFFERENCE IN THE PREVALENCE OF IgA-ASSOCIATED NEPHROPATHIES
SIR,-In Alabama, Blacks have a higher incidence of most major categories of renal disease, including glomerulonephritis, than
Whites.
The incidence of glomerular diseases that are characterised by the predominant deposition of IgA in the mesangium was not tabulated in that report. In our study of IgA nephropathy and Henoch-Schonlein purpura (HSP), two diseases which may be related,2we have noted a strikingly low prevalence of these glomerular diseases in our Black patients (table). Most of our patients (20/22) live in the region studied by Rostand et al,l and biopsies were done at the University of Alabama Medical Center or Children’s Hospital, Birmingham. A low prevalence of IgA 3 nephropathy among Blacks has also been noted in North Carolina,3 there were no Black in a and, Kentucky study of IgA nephropathy adults."* Studies on these IgA-associated diseases from Europe and Japan have not commented on race, probably because of the relative racial homogeneity in these regions. The racial distributions of admissions to our hospitals or of our patients subjected to kidney biopsy do not account for this finding. To the extent that the controversial linkage between HLA BW-35 and IgA nephropathy exists.5-7 the high BW-35 frequency of 29 - 7% for Blacks in this metropolitan area would, if anything, favour a high prevalence for IgA nephropathy in Blacks. Structural differences9 in IgA2 allotypes, which display a characteristic racial distribution (A2m(l) allotype predominates in Whites and A2m(2) in BlackslO) are probably irrelevant to IgA nephropathy. Although an initial report indicated the predominant deposition of the IgA2 subclass in glomeruli of patients with IgA nephropathy,llconcurrent and subsequent studies 12,13 with monoclonal IgA-subclass-specific antibodies convincingly demonstrated the deposition of molecules that belong to the IgAI subclass which are common to Blacks and Whites. All of our patients tested with a different set of monoclonal antibodies to IgA subclassesl4 also showed mesangial deposition ofIgAl but not IgA2.
rhenotype
JOHN H. GALLA
Departments of Medicine, Pediatrics, Pathology, and Microbiology, University of Alabama m Birmingham, Birmingham, Alabama 35294, USA
EDWARD C. KOHAUT RONALD ALEXANDER JIRI MESTECKY
1. Rostand SG, Kirk KA, Rutsky EA, Pate BA. Racial differences in the incidence of treatment for end-stage renal disease N EnglJ Med 1982, 306: 1276-79 2. Weiss JH, Bhathena DB, Curtis JJ, Lucas BA, Luke RG. A possible relationship between Henoch-Schonlein syndrome and IgA illustrative case Nephron 1978; 22: 582-91. 3 Jennette JC, Wall SD. The clinical and pathologic 4.
5.
nephropathy (Berger’s disease)
an
heterogeneity of IgA nephropathy Kidney 1983; 16: 17-23 Julian BA, Wyatt RJ, Mcmorrow RG, Galla JH. Serum complement proteins in IgA nephropathy. Clin Nephiol 1983; 20: 251-58. Berthoux FC, Gagne A, Sabatier JC, Ducans F, Le Pitf JC, Marcellos M, Merces B, Briam CP HLA-Bw35 and mesangial IgA glomerulonephritis N Engl J Med 1978, 298: 1034-35 R, Peters DK, Batchelon JR. Mesangial IgA glomerulonephritis and HLA antigens N Engl J Med 1979; 299: 200. Nagy J, et al. More on IgA glomerulonephritis and HLA antigens. N Engl J Med 1979. 300: 92. Barger BO Personal communication, 1983. Jerry LM, Kunkel HG, Grey HM. Absence of disulfide bonds linking the heavy and light chains: a property of genetic variant of gamma A2 globulins Proc Natl Acad Sci USA 1970, 64: 557. Wang AC, Fudenberg HH. Genetics and evaluation of human immunoglobulin A Adv
6 Brettle 7.
8. 9.
10.
Exp Med Biol 1974, 45: 161-65. C, Berthoux FC, André F, Gillon J, Yerin C, Sabatur J-C. Prevalence of IgA2 deposits in IgA nephropathies. N Engl J Med 1980; 303: 1343 Conley ME, Cooper MD, Michael AF. Selective deposition of immunoglobulin Al in immunoglobulin A nephropathy and systemic lupus erythematosus J Clin Invest
11. André 12.
1980; 66: 1432 Y, Edoh M, Nomoto Y, Sakai H. Immunoglobulin Al in IgA nephropathy N Engl J Med 1981, 305: 1159-60. 14. Crago SS, Kutteh WH, Moro I, Allansmith MR, Radl J, Haayman JJ, Mesteckv J
13. Tomino
Distribution of IgA1, IgA2, and Immunol 1984, 132: 16-18.
J-chain-containing
cells
in
human
tissues
J
SEASONALITY OF ULCERATIVE COLITIS man had exacerbations of distal ulcerative every winter for 8 years, and a 32-year-old woman had exacerbations of ileal Crohn’s disease during the spring of 8 successive years, except for a year when she was pregnant. Both required oral prednisolone during exacerbations only, and were well for the remainder of the year. In a postal survey of 100 patients (50 with ulcerative colitis and 50 with Crohn’s), 18 of 26 patients with ulcerative colitis who replied and 20 of 30 patients with Crohn’s disease who replied indicated by ticking a list of months that their disease was worse at a particular
SIR,-A 54-year-old
colitis
of diagnosis are in the experimental phase. In this case culture of half the biopsy sample avoided a late diagnosis and the stress and risk associated with a prostaglandin termination. We recommend this dual approach to first-trimester diagnosis of argininosuccinicaciduria and citrullinaemia, and it may well prove useful for other metabolic diseases. Paediatric Research
Unit,
Guy’s Hospital Medical School, London SE1 9RT
IgA-ASSOCIATED
DISEASES
C. M. VIMAL A. H. FENSOM
Cytogenetics Unit, St Mary’s Hospital Medical School, London W2
D. HEATON
Department of Obstetrics and Gynaecology, University College Hospital, London WC1
Faculty
R. H. T. WARD
of Clinical Sciences,
School of Medicine, University College London
P. GARROD
Galton Laboratory, Department of Genetics and Biometry, University College London
R.
J. A. PENKETH
Young EP, Patrick AD. First trimester diagnosis of metabolic diseases Prenatal Diagnosis Group News! 1983; 7 (Dec): 4-5. 2. Fensom AH, Jackson M, Sanguinetti N, et al. The use of chorionic villi for early prenatal diagnosis of metabolic disorders. J Med Genet 1984; 21: 142 (abstr). 3 Simoni G, Brambati B, Danesino C, et al Diagnostic application of first trimester trophoblast sampling in 100 pregnancies. Hum Genet 1984; 66: 252-59. 4. Tedesco TA, Mellman WJ. Argmmosuccinate synthetase activity and citrulline 1
*Percentages in parentheses. tlncludes Children’s Hospital for this period but excludes biopsies of transplanted kidneys.
metabolism in cells cultured from citrullinemic subjects. Proc Natl Acad Sci USA 1967; 57: 829-39 5. Fensom AH, Benson PF, Baker JE, Mutton DE Prenatal diagnosis of argininosuccinic aciduria: Effect of mycoplasma contamination on the indirect assay for argminosuccinate lyase. Am J Hum Genet 1980; 32: 761-63 6 Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent J Biol Chem 1951, 193: 265-75. 7. Ward RHT, Modell B, Petrou M, Karagozlu F, Douratsos E. Method of sampling
Notwithstanding these uncertainties, these observations regarding racial distribution support the notion that familial predisposition has an important role in the clinical expression of these common IgA-associated glomerular diseases.
chorionic villi in first trimester of pregnancy under guidance of real time ultrasound. Br Med J 1983; 286: 1542-44. 8. Heaton DE, Czepulkowski BH, Horwell DH, Coleman DV. Chromosome first trimester chorionic villus biopsies prepared by a maceration Prenatal Diagnosis 1984; 4: 279-87.
analysis of technique.
RACIAL DIFFERENCE IN THE PREVALENCE OF IgA-ASSOCIATED NEPHROPATHIES
SIR,-In Alabama, Blacks have a higher incidence of most major categories of renal disease, including glomerulonephritis, than
Whites.
The incidence of glomerular diseases that are characterised by the predominant deposition of IgA in the mesangium was not tabulated in that report. In our study of IgA nephropathy and Henoch-Schonlein purpura (HSP), two diseases which may be related,2we have noted a strikingly low prevalence of these glomerular diseases in our Black patients (table). Most of our patients (20/22) live in the region studied by Rostand et al,l and biopsies were done at the University of Alabama Medical Center or Children’s Hospital, Birmingham. A low prevalence of IgA 3 nephropathy among Blacks has also been noted in North Carolina,3 there were no Black in a and, Kentucky study of IgA nephropathy adults."* Studies on these IgA-associated diseases from Europe and Japan have not commented on race, probably because of the relative racial homogeneity in these regions. The racial distributions of admissions to our hospitals or of our patients subjected to kidney biopsy do not account for this finding. To the extent that the controversial linkage between HLA BW-35 and IgA nephropathy exists.5-7 the high BW-35 frequency of 29 - 7% for Blacks in this metropolitan area would, if anything, favour a high prevalence for IgA nephropathy in Blacks. Structural differences9 in IgA2 allotypes, which display a characteristic racial distribution (A2m(l) allotype predominates in Whites and A2m(2) in BlackslO) are probably irrelevant to IgA nephropathy. Although an initial report indicated the predominant deposition of the IgA2 subclass in glomeruli of patients with IgA nephropathy,llconcurrent and subsequent studies 12,13 with monoclonal IgA-subclass-specific antibodies convincingly demonstrated the deposition of molecules that belong to the IgAI subclass which are common to Blacks and Whites. All of our patients tested with a different set of monoclonal antibodies to IgA subclassesl4 also showed mesangial deposition ofIgAl but not IgA2.
rhenotype
JOHN H. GALLA
Departments of Medicine, Pediatrics, Pathology, and Microbiology, University of Alabama m Birmingham, Birmingham, Alabama 35294, USA
EDWARD C. KOHAUT RONALD ALEXANDER JIRI MESTECKY
1. Rostand SG, Kirk KA, Rutsky EA, Pate BA. Racial differences in the incidence of treatment for end-stage renal disease N EnglJ Med 1982, 306: 1276-79 2. Weiss JH, Bhathena DB, Curtis JJ, Lucas BA, Luke RG. A possible relationship between Henoch-Schonlein syndrome and IgA illustrative case Nephron 1978; 22: 582-91. 3 Jennette JC, Wall SD. The clinical and pathologic 4.
5.
nephropathy (Berger’s disease)
an
heterogeneity of IgA nephropathy Kidney 1983; 16: 17-23 Julian BA, Wyatt RJ, Mcmorrow RG, Galla JH. Serum complement proteins in IgA nephropathy. Clin Nephiol 1983; 20: 251-58. Berthoux FC, Gagne A, Sabatier JC, Ducans F, Le Pitf JC, Marcellos M, Merces B, Briam CP HLA-Bw35 and mesangial IgA glomerulonephritis N Engl J Med 1978, 298: 1034-35 R, Peters DK, Batchelon JR. Mesangial IgA glomerulonephritis and HLA antigens N Engl J Med 1979; 299: 200. Nagy J, et al. More on IgA glomerulonephritis and HLA antigens. N Engl J Med 1979. 300: 92. Barger BO Personal communication, 1983. Jerry LM, Kunkel HG, Grey HM. Absence of disulfide bonds linking the heavy and light chains: a property of genetic variant of gamma A2 globulins Proc Natl Acad Sci USA 1970, 64: 557. Wang AC, Fudenberg HH. Genetics and evaluation of human immunoglobulin A Adv
6 Brettle 7.
8. 9.
10.
Exp Med Biol 1974, 45: 161-65. C, Berthoux FC, André F, Gillon J, Yerin C, Sabatur J-C. Prevalence of IgA2 deposits in IgA nephropathies. N Engl J Med 1980; 303: 1343 Conley ME, Cooper MD, Michael AF. Selective deposition of immunoglobulin Al in immunoglobulin A nephropathy and systemic lupus erythematosus J Clin Invest
11. André 12.
1980; 66: 1432 Y, Edoh M, Nomoto Y, Sakai H. Immunoglobulin Al in IgA nephropathy N Engl J Med 1981, 305: 1159-60. 14. Crago SS, Kutteh WH, Moro I, Allansmith MR, Radl J, Haayman JJ, Mesteckv J
13. Tomino
Distribution of IgA1, IgA2, and Immunol 1984, 132: 16-18.
J-chain-containing
cells
in
human
tissues
J
SEASONALITY OF ULCERATIVE COLITIS man had exacerbations of distal ulcerative every winter for 8 years, and a 32-year-old woman had exacerbations of ileal Crohn’s disease during the spring of 8 successive years, except for a year when she was pregnant. Both required oral prednisolone during exacerbations only, and were well for the remainder of the year. In a postal survey of 100 patients (50 with ulcerative colitis and 50 with Crohn’s), 18 of 26 patients with ulcerative colitis who replied and 20 of 30 patients with Crohn’s disease who replied indicated by ticking a list of months that their disease was worse at a particular
SIR,-A 54-year-old
colitis