© 1991 S. Karger AG, Basel 0028-2766/91/059I- 0 I48S2.75/0
Nephron 1991;59:148-152
Homozygous C3 Deficiency Associated with IgA Nephropathy Keizo Imaia . Keiko Nakajima a , Kazuhiko Eguchia , Masanobu Miyazakia , Masayuki Endoir', Yasuhiko Tominoa . Yasuu Nomoto*, Hideto Sakai*, Yukio Hyodob “Department of Internal Medicine, School of Medicine, Tokai University, Isehara: bDepartment of Infection and Immunology, Kanagawa Children’s Medical Center, Yokohama, Kanagawa, Japan
Key Words. C3 deficiency • IgA nephropathy
Introduction Genetic absence of the third component of comple ment (C3) is rare and its immunopathologic manifesta tions are of potential scientific interest. Most cases showed repeated bacterial infections [1-11]. Complement deficiency may predispose to the development of im mune complex glomerulonephritis because the clearance of the immune complex may be impaired in such condi tion. In this report, we describe a patient with homozy gous C3 deficiency who developed IgA nephropathy, and discuss the literature concerning C3 deficiency and glomerulonephritis. Case Report A 23-year-old male patient was admitted to the Tokai University Hospital for the first time on June 5, 1987, because of persistent proteinuria and microhematuria since 1984. He had experienced an
episode of meningitis at the age of 4 and had been having a history of hypertension since the age of 21. In the family history, one of his female cousins had homozygous deficiency of the third complement component and systemic lupus erythematosus without overt ne phropathy. He was also found to have homozygous C3 deficiency in a family study at the age of 16 without any symptoms at that time. The pedigree is shown in figure 1. Physical examination on admission revealed a well-developed and well-nourished male. Blood pressure was 146/90 mm Hg. No skin rash, lymphadenopathy or joint deformity was found. The tonsils were slightly enlarged. The lungs, heart and abdomen were normal. There was no peripheral edema. Neurological examination was negative. Urinalysis revealed 3 + protein and 2+ occult blood. There were 1-4 red blood cells and 1-4 leukocytes per high power field, and 5-6 hyaline casts per total fields in the urinary sediment. Quantitation of urinary protein showed excretion of 0.44 g/day. Serum creatinine was 1.2 mg/dl, blood urea nitrogen 12 mg/dl, and uric acid 7.7 mg/dl. Whole blood count was normal (table I). Serum levels of IgG, IgA and IgM were 1,200 mg/dl, 300 mg/dl and 133 mg/dl, respectively. Serum antinuclear antibody and rheuma toid factor were negative. Serum levels of C3 were measured by laser nephelometry and hemolytic complement activity was determined by Mayer's method, but there were no detectable amounts (table I).
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 3:33:20 AM
Abstract. A 23-year-old male patient with homozygous C3 deficiency who developed asymptomatic proteinuria and hematuria was reported. Renal biopsy disclosed typical IgA nephropathy with deposition of early- and late-complement components except for C3 deposition. C9 and membrane attack complex were detected in the glomeruli despite the absence of C3. It was suggested that there might be some unknown complement activation mechanism which does not require C3 component.
149
Homozygous C3 Deficiency Associated with IgA Nephropathy
Table 1. Laboratory data
3 + (0.44 g/day) + 1-4/HPF 1-4/HPF 5-6/total 545 x lOVmm3 16.5 48.5 % 7.000 mmJ 60% 1% 24% 6% 9% 24.2 x lOVmm3 4.7 g/dl 6.8 g/dl 79 mg/dl 12 mg/dl 1.2 mg/dl
Fig. 1. Pedigree.
Radiography and ultrasonography of his kidneys showed no abnormalities. An open renal biopsy was performed on June 19,1987, to disclose the precise cause of proteinuria. Light-microscopic examination of the biospy specimen showed slight proliferation of glomerular mes angial cells with a slight increase in the matrix, focally and segmentally (fig. 2). No clearly thickened capillary walls were observed. The
UA Na K Cl GOT GPT LDH Immunological test CRP ASO ASK IgG IgA IgM C3 C4 CH50 RA test ANA anti DNA Renal function PSP GFR Serum pr microglobulin Urinary p2-microglobulin
7.7 mg/dl 144 mg/dl 4.9 mg/dl 105 mg/dl 24 IU/1 58 IU/I 178 1U/I -
1:60 1:40 1.200 mg/dl 300 mg/dl 133 mg/dl < Im g/dl 24 mg/dl
Nephron 1991;59:148-152
Homozygous C3 Deficiency Associated with IgA Nephropathy Keizo Imaia . Keiko Nakajima a , Kazuhiko Eguchia , Masanobu Miyazakia , Masayuki Endoir', Yasuhiko Tominoa . Yasuu Nomoto*, Hideto Sakai*, Yukio Hyodob “Department of Internal Medicine, School of Medicine, Tokai University, Isehara: bDepartment of Infection and Immunology, Kanagawa Children’s Medical Center, Yokohama, Kanagawa, Japan
Key Words. C3 deficiency • IgA nephropathy
Introduction Genetic absence of the third component of comple ment (C3) is rare and its immunopathologic manifesta tions are of potential scientific interest. Most cases showed repeated bacterial infections [1-11]. Complement deficiency may predispose to the development of im mune complex glomerulonephritis because the clearance of the immune complex may be impaired in such condi tion. In this report, we describe a patient with homozy gous C3 deficiency who developed IgA nephropathy, and discuss the literature concerning C3 deficiency and glomerulonephritis. Case Report A 23-year-old male patient was admitted to the Tokai University Hospital for the first time on June 5, 1987, because of persistent proteinuria and microhematuria since 1984. He had experienced an
episode of meningitis at the age of 4 and had been having a history of hypertension since the age of 21. In the family history, one of his female cousins had homozygous deficiency of the third complement component and systemic lupus erythematosus without overt ne phropathy. He was also found to have homozygous C3 deficiency in a family study at the age of 16 without any symptoms at that time. The pedigree is shown in figure 1. Physical examination on admission revealed a well-developed and well-nourished male. Blood pressure was 146/90 mm Hg. No skin rash, lymphadenopathy or joint deformity was found. The tonsils were slightly enlarged. The lungs, heart and abdomen were normal. There was no peripheral edema. Neurological examination was negative. Urinalysis revealed 3 + protein and 2+ occult blood. There were 1-4 red blood cells and 1-4 leukocytes per high power field, and 5-6 hyaline casts per total fields in the urinary sediment. Quantitation of urinary protein showed excretion of 0.44 g/day. Serum creatinine was 1.2 mg/dl, blood urea nitrogen 12 mg/dl, and uric acid 7.7 mg/dl. Whole blood count was normal (table I). Serum levels of IgG, IgA and IgM were 1,200 mg/dl, 300 mg/dl and 133 mg/dl, respectively. Serum antinuclear antibody and rheuma toid factor were negative. Serum levels of C3 were measured by laser nephelometry and hemolytic complement activity was determined by Mayer's method, but there were no detectable amounts (table I).
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/4/2018 3:33:20 AM
Abstract. A 23-year-old male patient with homozygous C3 deficiency who developed asymptomatic proteinuria and hematuria was reported. Renal biopsy disclosed typical IgA nephropathy with deposition of early- and late-complement components except for C3 deposition. C9 and membrane attack complex were detected in the glomeruli despite the absence of C3. It was suggested that there might be some unknown complement activation mechanism which does not require C3 component.
149
Homozygous C3 Deficiency Associated with IgA Nephropathy
Table 1. Laboratory data
3 + (0.44 g/day) + 1-4/HPF 1-4/HPF 5-6/total 545 x lOVmm3 16.5 48.5 % 7.000 mmJ 60% 1% 24% 6% 9% 24.2 x lOVmm3 4.7 g/dl 6.8 g/dl 79 mg/dl 12 mg/dl 1.2 mg/dl
Fig. 1. Pedigree.
Radiography and ultrasonography of his kidneys showed no abnormalities. An open renal biopsy was performed on June 19,1987, to disclose the precise cause of proteinuria. Light-microscopic examination of the biospy specimen showed slight proliferation of glomerular mes angial cells with a slight increase in the matrix, focally and segmentally (fig. 2). No clearly thickened capillary walls were observed. The
UA Na K Cl GOT GPT LDH Immunological test CRP ASO ASK IgG IgA IgM C3 C4 CH50 RA test ANA anti DNA Renal function PSP GFR Serum pr microglobulin Urinary p2-microglobulin
7.7 mg/dl 144 mg/dl 4.9 mg/dl 105 mg/dl 24 IU/1 58 IU/I 178 1U/I -
1:60 1:40 1.200 mg/dl 300 mg/dl 133 mg/dl < Im g/dl 24 mg/dl
