Abstract
To determine the origin of the increased serum ferritin that occurs in adult Still's disease (ASD), we analyzed subunits of the serum ferritin as follows. Gel filtration with Sepharose CL-6B demonstrated that the molecular weight of serum ferritin was about 490 kDa. Western blot analysis revealed only L-subunits (molecular weight 19 kDa) in patients with serum ferritin levels higher than 1.000 ng/ml. Patients with serum ferritin levels lower than 1,000 ng/ml, however, showed G-subunits (molecular weight 23 kDa) in addition to the L-subunits. When concanavalin A (Con-A) Sepharose 4B was used in an absorption test, the percentage absorption was extremely low in the patients with serum ferritin levels higher than 1,000 ng/ml. Isoferritin patterns of the patients determined by chromatofocusing revealed traces of acidic ferritin. The findings suggested that glycosylated ferritin does not account for the major portion of the increased serum ferritin.
Similar content being viewed by others
References
Bywaters EGL (1971) Still's disease in the adult. Ann Rheum Dis 30: 121–133
Ota T, Higashi S, Suzuki H, Eto S (1987) Increased serum ferritin levels in adult Still's disease. Lancet I: 562–563
Ota T, Higashi S, Masuda M, Tanaka Y, Saito K, Eto S, Suzuki H (1990) Serum ferritin as a useful test for diagnosis of adult Still's disease. Jpn J Rheumatol 2: 119–125
Ohta A, Yamaguchi M, Tsunematsu T, Kasukawa R, Mizushima H, Kashiwagi H, Kashiwazaki S, Tanimoto K, Matsumoto Y, Akizuki M, Ota T (1990) Adult Still's disease: a multicenter survey of Japanese patients. J Rheumatol 17: 1058–1063
Blake DR, Bacon PA (1981) Synovial fluid ferritin in rheumatoid arthritis. BMJ 282: 189
Biemond P, Swaak AJG, van Eijk HG, Koster JF (1983) Intraarticular ferritin-bound iron in rheumatoid arthritis. Arthritis Rheum 29: 1187–1193
Cragg SJ, Wagstaff M, Worwood M (1981) Detection of a glycosylated subunit in human serum ferritin. Biochem J 199: 565–571
Yamaguchi M, Ohta A, Tsunematsu T, Kasukawa R, Mizushima Y, Kashiwagi H, Kashiwazaki S, Tanimoto K, Matsumoto Y, Ota T, Akizuki M (1992) Preliminary criteria for classification of adult Still's disease. J Rheumatol 19:424–430
Zuyderhoudt FMJ, Boers W, Linthorst C, Jorning GGA, Hengeveld P (1978) An enzyme-linked immunoassay for ferritin in human serum and rat plasma and influence of the iron in serum ferritin on serum ferritin on serum iron measurement during acute hepatitis. Clin Chim Acta 88: 37–44
Woorwood M, Cragg SJ, Wagstaff M, Jacobs A (1979) Binding of human serum ferritin to concanavalin A. Clin Sci 56: 83–87
Shwarz-Eywill M, Heilig B, Bauer H, Breitbart A, Pezzutto A (1992) Evaluation of serum ferritin as a merker for adult Still's disease activity. Ann Rheum Dis 51: 683–685
Pelkonen P, Swanljung K, Siimes MA (1986) Ferritinemia as an indicator of systemic disease activity in children with systemic juvenile rheumatoid arthritis. Acta Paediatr Scand 75: 64–68
Biemond P, van Eijk HG, Swaak AJG, Koster JF (1984) Iron mobilization from ferritin by superoxide derived from stimulated polymorphonuclear leukocytosis. J Clin Invest 73: 1576–1579
Santambrogio P, Cozzi A, Levi S, Arosio PP (1987) Human serum ferritin G-peptide is recognized by anti-L ferritin subunit antibodies and concanavalin-A. Br J Haematol 65: 235–237
Broxmeyer HE, Gentile P, Bognaki H, Ralph P (1983) Lactoferrin, transferrin and acidic isoferritins: regulatory molecules with potential therapeutic value in leukemia. Blood Cells 9: 83–105
De Sousa M, Smithyman A, Tan C (1978) Suggested models of ecotaxopathy in lymphoreticular malignancy: a role for iron binding proteins in the control of lymphoid cell migration. Am J Pathol 90: 497–520
Hahncock SW, Bruce L, May K (1979) Ferritin: sensitizing substance in the leukocyte migration inhibition test in patients with malignant lymphoma. Br J Haematol 43: 229–233
McKeering LV, Halliday JW, Caffin J, Mack U, Powel L (1976) Immunological detection on isoferritins in normal human serum and tissue. Clin Chim Acta 67: 189–197
Yoshino Y, Linpisarn S, Makonkawkeyoon L, Hirai Y, Hisayasu S, Orimo H, Kuga M, Sanguansermsri T (1987) Serum ferritin and its isoferritin patterns in homozygous β-thalassemia. Acta Haematol Jpn 50:766–776
Esumi N, Ikushima S, Hibi S, Todo S, Imashuku S (1988) High serum ferritin level as a marker of malignant histiocytosis and virus-associated hemophagocytic syndrome. Cancer 61: 2071–2076
Hann HWL, Stahlhut MW, and Evans AE (1986) Source of increased ferritin in neuroblastoma: studies with concanavalin-A sepharose binding. J Natl Cancer Inst 76: 1031–1033
Prieto J, Barry M, Sherlock S (1975) Serum ferritin in patients with iron overload and acute and chronic liver diseases. Gastroenterology 68: 525–533
Milman N, Graudal N (1984) Serum ferritin in acute viral hepatitis. Scand J Gastroenterol 19: 38–40
Jacobs A, Worwood M (1975) Ferritin in serum: clinical and biochemical implications. N Engl J Med 292: 951–956
Rogers JT, Bridges KR, Durmowicz GP, Glass J, Auron PE, Munro HN (1990) Translational control during the acute phase response. J Biol Chem 265: 14572–14578
Tsuji Y, Miller LL, Miller SC, Torti SV, Torti FM (1991) Tumor necrosis factor-α and interleukin 1-α regulate transferrin receptor in numan diploid fibroblast. J Biol Chem 266: 7257–7261
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Higashi, S., Ota, T. & Eto, S. Biochemical analysis of ferritin subunits in sera from adult Still's disease patients. Rheumatol Int 15, 45–50 (1995). https://doi.org/10.1007/BF00262707
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00262707