This paper is only available as a PDF. To read, Please Download here.
Abstract
During a 40 month interval, 35 patients were seen with a plasma cell dyscrasia in
which the only detectable monoclonal immunoglobulin abnormality consisted of excess
production of either type kappa or type lambda light chains (Bence Jones protein).
This group constituted 17.3 per cent of the total number of patients with plasma cell
dyscrasias and 25.7 per cent of the patients with myeloma identified during the same
period. Variable initial clinical presentation, the absence of a typical monoclonal
serum spike and the unreliability of commonly used urine protein tests made recognition
of the disorder difficult in many patients. Sulfosalicylic acid and p-toluene sulfonic
acid proved valuable in screening for urine protein. Definition of “proteinuria” by
quantitative, electrophoretic and immunochemical studies was essential for diagnosis.
Bence Jones proteinemia was present in 80 per cent of the patients; panhypogammaglobulinemia
and lytic bone lesions were demonstrable in more than 60 per cent. Although no specific
morphologic abnormality of marrow plasma cells was evident by light microscopy, the
absence of rouleau on peripheral blood smear was a helpful diagnostic clue. Although
patients with lambda light chains presented with more Bence Jones proteinuria, this
did not correlate with the severity of initial renal functional impairment or with
survival when compared to patients with kappa light chains. No other clinical or laboratory
observation differentiated the groups with kappa light chains from those with lambda
light chains. Amyloid was identified in seven patients. Their course was dominated
by the features of primary systemic amyloidosis instead of the usual findings of classic
myeloma. Patients with amyloidosis had lower initial serum albumin levels, fewer lytic
bone lesions and reduced survival compared to patients without amyloidosis.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to The American Journal of MedicineAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Plasma cell dyscrasias. Current clinical and biochemical concepts.Am J Med. 1968; 44: 256
- Diagnosis and Treatment of Multiple Myeloma.Grune & Stratton, New York1970
- Multiple myeloma and related plasma cell dyscrasias.(chap 26)in: Samter M Immunological Diseases. Little, Brown & Co, Boston1971
- Myelomatosis.University Park Press, Baltimore1971
- Plasma cell myeloma.(chap 114)in: Hematology. McGraw-Hill, New York1972
- Multiple Myeloma and Related Disorders. vol 1. Harper & Row, Hagerstown1973
- Metabolism of Bence Jones proteins.J Clin Invest. 1964; 43: 103
- Bence Jones proteinemia.Am J Med. 1964; 37: 206
- Double spike in myeloma serum due to retention of light chains.Arch Intern Med. 1969; 124: 77
- Light-chain disease. An abortive variant of multiple myeloma.Ann Intern Med. 1966; 65: 471
- A Primer of Urinalysis.in: Hoeber Medical Division, Harper & Row, New York1963: 27
- Detection of urinary Bence Jones protein by means of p-toluene sulfonic acid (TSA).Am J Clin Pathol. 1963; 37: 660
- Diagnostic Laboratory Hematology.in: Grune & Stratton, New York1968: 411
- Variation of protein content of urine in a 24-hour period.Clin Chem. 1963; 9: 63
- Determination of Bence Jones protein in the urine.JAMA. 1960; 173: 1137
- Studies on monoclonal antibodies. I. The specificity and binding properties of a Waldenström macroglobulin with anti-γG activity.J Lab Clin Med. 1973; 81: 393
- Quantitative determination of serum immunoglobulins in antibody-agar plates.J Immunol. 1965; 94: 84
- Immunoelectrophoretic characterization of the serum and urinary proteins in plasma cell myeloma and Waldenström's macroglobulinemia.Ann NY Acad Sci. 1961; 94: 93
- Immunoglobulin disturbances and their clinical significance.Med Clin North Am. 1973; 57: 499
- Amyloidosis.N Engl J Med. 1967; 277: 522
- Amyloidosis.N Engl J Med. 1967; 277: 574
- Amyloidosis.N Engl J Med. 1967; 277: 628
- Acute anuria following intravenous pyelography in a patient with myelomatosis.Acta Med Scand. 1954; 150: 297
- Acute renal failure after intravenous pyelography in plasma cell myeloma.JAMA. 1958; 167: 2186
- The effect of urography on renal function in patients with multiple myeloma.Can Med Assoc J. 1964; 91: 786
- Factors in the renal failure of multiple myeloma.Arch Intern Med. 1965; 116: 400
- Anuria following urography with meglumine diatrizoate (Renografin) in multiple myeloma.Radiology. 1968; 90: 780
- Bone lesions in primary systemic amyloidosis. A report of a case.Br J Radiol. 1961; 34: 778
- Bone lesions in primary amyloidosis.Am J Roentgenol Radium Ther Nucl Med. 1967; 101: 872
- Amyloid arthritis simulating rheumatoid disease in five patients with multiple myeloma.Am J Med. 1973; 55: 142
- Treatment for multiple myeloma. Combination chemotherapy with different melphalan dose regimens.JAMA. 1969; 208: 1680
- N Engl J Med. 1972; 286: 1256
- Sarcoidosis of the skull.Ann Intern Med. 1970; 72: 929
- Pseudomyeloma.Radiology. 1970; 95: 41
- Pathologic conditions associated with plasma cell dyscrasias. A study of 806 cases.Ann NY Acad Sci. 1971; 190: 507
- A “protein error”.Lancet. 1964; 1: 1248
- Bence-Jones protein: detection and implications.N Engl J Med. 1974; 290: 106
- The heat precipitation of Bence Jones proteins. I. Optimum conditions.Arch Biochem Biophys. 1959; 83: 115
- Urinary light-chain excretion in myeloma and other disorders—an evaluation of the Bence-Jones test.J Lab Clin Med. 1968; 71: 812
- Urine transferrin masquerading as Bence Jones protein (BJP) in the nephrotic syndrome of primary amyloidosis.Clin Res. 1974; 22: 529A
- The Roentgenological Features of Sickle Cell Disease and Related Hemoglobinopathies.in: Charles C Thomas, Springfield, Ill1965: 99
- Frequency of pathological proteins (M-components) in 6,995 sera from an adult population.Acta Med Scand. 1966; 179: 235
- Dysimmunoglobulinemia in the absence of clinical features of multiple myeloma and macroglobulinemia.Am J Med. 1967; 42: 67
- Paraproteins, benign or malignant?.Br Med J. 1967; 3: 699
- Thirty cases of monoclonal immunoglobulin disorders other than myeloma or macroglobulinemia.Am J Med. 1969; 46: 562
- Studies of “benign” serum M-components.Am J Med Sci. 1969; 257: 275
- Dysimmunoglobulinemia associated with hepatobiliary disorders.Am J Med. 1970; 48: 196
- Natural history of monoclonal immunoglobulins. (myeloma workshop).in: Br Med J. 2. 1971: 321
- Diffuse (nonmyelomatous) plasmacytosis with dysproteinemia.Am J Clin Pathol. 1968; 50: 302
- Monoclonal gammopathy. Study of 52 cases.NZ Med J. 1970; 72: 383
- Immunocytoma o' mice and men.Br Med J. 1971; 2: 67
- Nonmyelomatous monoclonal immunoglobulinemia.Prog Clin Immunol. 1972; 1: 105
- Abnormal peripheral vascular dynamics in systemic amyloidosis.Ann Intern Med. 1969; 70: 1167
- Bence-Jones-Eiweiss und Amyloid.Z Klin Med. 1931; 116: 510
- Die Paraproteinosen. Über die Störung des Eiweiss-stoffwechsels bei Plasmocytom.Virchows Arch Path Anat. 1940; 306: 631
- Amyloidosis in multiple myeloma. Progress noted in 50 years of personal observation.J Mt Sinai Hosp. 1952; 19: 8
- Metabolic abnormalities in multiple myeloma.(chap 6)in: Multiple Myeloma. Grune & Stratton, New York1953
- “Primary” systemic amyloidosis and myeloma. Discussion of relationship and review of 81 cases.Arch Intern Med. 1961; 107: 344
- The pathogenesis of “amyloidosis”.in: Sem Hematol. 1. 1964: 3
- Amyloid fibril proteins. Proof of homology with immunoglobulin light chains by sequence analyses.Science. 1971; 172: 1150
- Creation of “amyloid” fibrils from Bence Jones proteins in vitro.Science. 1971; 174: 712
- Bence-Jones proteinemia in multiple myeloma.J Clin Invest. 1943; 22: 67
- A case of tetramer Bence Jones proteinemia.Clin Exp Immunol. 1968; 3: 277
- IgG myeloma with closed tetrameric Bence Jones proteinemia.Am J Med. 1969; 47: 978
- Primary amyloidosis with plasmacytic dyscrasia and a tetramer of Bence Jones type lambda globulin in the serum and urine.Blood. 1971; 37: 473
- Protein-protein interactions among L polypeptide chains of Bence Jones proteins and human γ-globulins.J Exp Med. 1964; 119: 817
- Polymerism, polymorphism and impurities in Bence-Jones proteins.Biochim Biophys Acta. 1964; 86: 295
- Physicochemical properties of Bence-Jones proteins in the form of L-chain dinners.Biochim Biophys Acta. 1965; 94: 175
- Proteinuria in multiple myeloma.Ciln Sci. 1966; 31: 95
- The renal handling of low molecular weight proteins. II. Disorders of serum protein catabolism in patients with tubular proteinuria, the nephrotic syndrome, or uremia.J Clin Invest. 1972; 51: 2162
- The immunoglobulin origin of amyloid.Am J Med. 1972; 52: 141
- Amyloid disease of the liver. Correlation of clinical, functional and morphologic features in 47 patients.Am J Med. 1962; 33: 349
- A clinical analysis of the course and prognosis of 42 patients with amyloidosis.Am J Med. 1968; 44: 955
- Primary amyloidosis. Clinical, immunochemical and immunoglobulin metabolism studies in 15 patients.Am J Med. 1969; 47: 259
- Orthostatic hypotension as a clue to primary systemic amyloidosis.Circulation. 1966; 34: 883
- Systemic amyloidosis, functional coronary insufficiency and autonomic impairment.Ann Intern Med. 1972; 76: 599
- Peripheral and autonomic nerve involvement in primary amyloidosis associated with uncontrollable diarrhoea and steatorrhoea.Am J Med. 1965; 39: 277
- Abnormal respiratory control in acquired dysautonomia.N Engl J Med. 1971; 285: 366
- Functional asplenia in sickle-cell anemia.N Engl J Med. 1969; 281: 923
- Adult coeliac disease in hyposplenic patients.Lancet. 1970; 1: 163
- Statistics in Research.in: Iowa State University Press, Ames1963: 124
- The treatment of multiple myeloma.in: Sem Hematol. 10. 1973: 149
- Regression models and life-tables.J Roy Statist Soc(B). 1972; 34: 187
- Morphology and protein synthesis in multiple myeloma and macroglobulinemia.Ann NY Acad Sci. 1964; 113: 642
- “Intermediate” cell types and mixed cell proliferation in multiple myeloma. Electron microscopic observations.Blood. 1966; 27: 212
- Fractionation of serum proteins in hyperproteinemia, with special reference to multiple myeloma.J Clin Invest. 1941; 20: 765
- The frequency of kappa and lambda chains in pathologic serum γG, γA, γD and γμ immunoglobulins.Scand J Haematol. 1967; 4: 46
- Immunochemical classes of myelomatosis.Br J Hematol. 1969; 16: 599
- The relationship between L-chain synthesis and γ-globulin production.J Clin Invest. 1973; 52: 1067
- Normal counterparts to Bence Jones proteins. Free L polypeptide chains of human γ-globulin.in: Proc Natl Acad Sci. 49. 1963: 330
- Urinary light chain excretion in leukemia and lymphoma.Clin Exp Immunol. 1969; 5: 83
- Plasma proteins in normal human urine.in: Manuel Y. Revillard J.P. Betuel H. Proteins in Normal and Pathological Urine. University Park Press, Baltimore1970: 7
- Serum and urinary gamma globulins in rheumatoid arthritis.Trans Assoc Am Physicians. 1963; 76: 222
- Serum sickness. Evidence in man of antigen-antibody complexes and free light chains in the circulation during the acute reaction.ANN Intern Med. 1967; 67: 596
- Immunologic events preceding clinical exacerbation of systemic lupus erythematosus.Am J Med. 1973; 54: 631
- Effect of renal homotransplantation on the metabolism of the light chains of immunoglobulins.Ann Intern Med. 1968; 68: 48
- Bence Jones proteinuria in benign monoclonal gammopathies.Acta Med Scand. 1968; 184: 403
- Malignant lymphoma and lymphatic leukemia associated with myeloma-type serum proteins.Am J Med. 1957; 23: 239
- Application of a modified technique to study urinary immunoglobulin light chain and whole IgG excretion in normal human subjects and patients with immune-related disorders.J Lab Clin Med. 1970; 75: 636
- Lymphosarcoma with Bence Jones proteinuria (type K) and IgG serum M-component (type L). A bitypic gammopathy.in: Mayo Clin Proc. 45. 1970: 413
- Light chain disease (hypogammaglobulinemia and Bence Jones proteinuria) and sideroblastic anemia-preleukemic chronic granulocytic leukemia.Canad Med Assoc J. 1972; 106: 995
- Immunological abnormalities in juvenile myelomonocytic leukemia.Br Med J. 1973; 1: 71
- Acute myelomonocytic leukemia with macroglobulinemia, Bence Jones proteinuria, and hypercalcemia.Cancer. 1973; 32: 121
- “Benign” monoclonal gammopathy. A potentially malignant condition?.Am J Med. 1966; 40: 426
- Report on the first myelomatosis trial. I. Analysis of presenting features of prognostic importance.Br J Haematol. 1973; 24: 123
- Growth rates and response to treatment in human myelomatosis.Br J Hematol. 1969; 16: 607
- Mutagenesis of mouse myeloma cells with “melphalan”.Nature (Lond). 1973; 245: 320
- Idiopathic Bence Jones proteinuria—a distinct entity?.Am J Med. 1973; 55: 222
- Plasmacytic myeloma. A study of the relationship of survival to various clinical manifestations and anomalous protein type in 112 patients.Am J Med. 1967; 42: 937
- Proposed guidelines for protocol studies. II. Plasma cell myeloma.Cancer Chemother Rep. 1968; 1: 17
- Amyloidosis and multiple myeloma. A reevaluation using a control population.Am J Med. 1973; 54: 166
- Melphalan and prednisone. An effective combination for the treatment of multiple myeloma.Am J Med. 1973; 54: 589
- The role of the kidney in the catabolism of Bence Jones proteins and immunoglobulin fragments.J Exp Med. 1967; 126: 207
- Renal handling of low molecular weight proteins. I. L-chain metabolism in experimental renal disease.J Clin Invest. 1971; 50: 901
- Acute renal failure in multiple myeloma.Am J Med. 1968; 44: 128
- Chronic hemodialysis in myelomatosis.Ann Intern Med. 1972; 77: 239
- Amyloidosis, multiple myeloma, and Waldenström's macroglobulinemia.(chap 20)in: Pathology of the Kidney. Little, Brown & Co, Boston1966
- Renal involvement in myeloma, amyloidosis, systemic lupus erythematosus, and other disorders of connective tissue.(chap 21)in: Strauss M.B. Welt L.G. Diseases of the Kidney. Little, Brown & Co, Boston1971
- Effect of sustained diuresis on the renal lesions of mice with Bence Jones protein-producing tumors.J Lab Clin Med. 1974; 83: 409
- Immunofluorescent studies of the myeloma kidney with special reference to light chain disease.Am J Med. 1968; 44: 922
- Multiple myeloma and the adult Fanconi syndrome.Am J Med. 1957; 22: 5
- Multiple myeloma with the Fanconi syndrome.Am J Med. 1963; 34: 125
- The adult Fanconi syndrome.Medicine. 1972; 51: 107
- Role of Bence Jones and other urinary proteins in renal dysfunction.J Clin Invest. 1971; 50: 74a
- Bence Jones proteinuria and renal failure in multiple myeloma.Clin Res. 1974; 22: 486A
- The nephrotic syndrome.(chap 16)in: Strauss M.B. Welt L.G. Diseases of the Kidney. Little, Brown & Co, Boston1971
- The nephrotic syndrome: current concepts.Ann Intern Med. 1972; 76: 463
- Multiple myeloma with massive proteinuria and terminal renal failure.Am J Med. 1972; 52: 538
- Immunoglobulins and amyloidosis.Am J Med. 1972; 52: 93
- Patterns of amyloidosis and their association with plasma-cell dyscrasia, monoclonal immunoglobulins and Bence-Jones proteins.N Engl J Med. 1974; 290: 473
- Bence-Jones proteins and light chains of immunoglobulins. I. Formation and characterization of amino-terminal (variant) and carboxyerminal (constant) halves.J Biol Chem. 1969; 244: 3393
- Low-molecular-weight proteins related to Bence Jones proteins in multiple myeloma.Science. 1966; 151: 1237
- Polymer formation during the degradation of human light chain and Bence-Jones proteins by an extract of the lysosomal fraction of normal human kidney.Immunochemistry. 1972; 9: 9
- On a new substance occurring in the urine of a patient with mollities ossium.Philos Trans R Soc Lond (Biol Sci). 1848; 138: 55
- Electron microscopic analysis of isolated amyloid fibrils from patients with primary, secondary and myeloma-associated disease.Isr J Med Sci. 1973; 9: 849
- Amyloidosis and immunoglobulins.Adv Intern Med. 1974; 19: 41
- Structural identity of Bence Jones and amyloid fibril proteins in a patient with plasma cell dyscrasia and amyloidosis.J Clin Invest. 1973; 52: 1276
- Current concepts of amyloid.Adv Immunol. 1972; 15: 249
- Amyloidosis: its nature and pathogenesis.in: Sem Hematol. 10. 1973: 65
- Immunoglobulin and amyloid fibril proteins.Br J Haematol. 1973; 24: 533
- Fibrillar assemblage of variable segments of immunoglobulin light chains. An electron microscopic study.J Immunol. 1973; 110: 21
- The amino acid sequence of a major nonimmunoglobulin component of some amyloid fibrils.J Clin Invest. 1972; 51: 2773
- Immunologic studies of the major nonimmunoglobulin protein of amyloid. I. Identification and partial characterization of a related serum component.J Exp Med. 1973; 138: 373
- Immunoglobulin synthesis and tumor kinetics of multiple myeloma.in: Sem Hematol. 10. 1973: 135
- Acceleration of casein induced amyloidosis in mice by immunosuppressive agents.Acta Pathol Microbiol Scand [A]. 1971; 79: 61
- Treatment of “primary” renal amyloidosis with melphalan.Lancet. 1972; 2: 616
Article info
Publication history
Accepted:
June 4,
1974
Footnotes
☆Portions of this study were presented at the 53rd Annual Meeting of the American College of Physicians, Atlantic City, New Jersey, April 1972 (Ann Intern Med 76: 871, 1972) and at the National Meeting of the American Federation for Clinical Research, Atlantic City, New Jersey, April 1973 (Clin Res 21:655, 1973). This study was supported by Grant ET-62 from the American Cancer Society, the Damon Runyon Memorial Fund, and the Texas Heart Association. This work was performed during the tenure of an Established Investigatorship of the American Heart Association (M.J.S.).
Identification
Copyright
© 1975 Published by Elsevier Inc.
