Familial immunopathies.Report of nine families and survey of literature

Abstract

Nineteen individuals are reported who represent nine familial instances of various immunopathies. Multiple myeloma was diagnosed in 10 members of five families, lanthanic (idiopathic) paraproteinemia in five members of two families and either myeloma or lanthanic paraproteinemia in four members of the remaining two families. The parent-child relationship occurred in three instances, siblings were affected in three, and first cousins in three families. Immunochemical studies revealed IgG paraprotein in nine cases; IgA in three; IgMl type in three subjects belonging to the same family; Bence-Jones protein in one case and biclonal paraproteinemia, IgGk plus IgAl in one. Three individual cases of lanthanic paraproteinemia, discovered in a prospective study of 76 relatives of subjects with immunopathies, suggest that there may be a higher frequency of immunopathies among family members than observed in the general population of comparable age. The published reports on familial paraproteinemias are reviewed.Cancer 40 families with multiple myeloma and related conditions. The results of studies performed on relatives of other patients with various paraproteinemias are included. MATERIALS AND METHODSThe data in these studies were collected over 9 years; the protein analyses were carried out at the Veterans Administration Hospital, Pittsburgh, and, in the relatives of family VII, at the Protein Study Center of The Memorial Hospital, Pawtucket, Rhode Island. In addition to the 29 relatives of families 1-111, VI and VII, a group of 82 close relatives of other patients with various immunocytic dyscrasias was included in these studies. Serum protein examinations consisted of electrophoresis on cellulose acetate membranes; immunoelectrophoresis was done by Scheidegger's micromodification method, quantitative immunoglobulin determination by the immunoplate method, 36 rheumatoid factor by latex fixation, and total serum proteins by a standard technique. Bence Jones protein in urine was evaluated by Snapper's heat test6'and by electrophoresis of concentrated urine. The monoclonal proteins were identified with commercially available monospecific antisera. TerminologyLanthanic paraproteinemia is used in this paper in preference to such expressions as "pre- 2094

Genetic and immune-related factors in the pathogenesis of lymphoproliferative and plasma cell malignancies

“…There is evidence to support a role for genetic factors, including studies showing familial aggregation of MM 3,17,[33][34][35][36][37][38] and familial aggregation of MGUS. 18 In addition, racial disparities in incidence patterns for MGUS and MM support a role for germ-line genes in the etiology of MM.…”

Familial myeloma and monoclonal gammopathy: A report of eight African American families

“…There have been many reports of the familial occurrence of myeloma in the literature, implying a hereditary element or a common environmental factor [11][12][13][14][15][16]. Most of these families have been of Caucasian origin.…”

“…Brown et al [8] found that cigarette smoking and alcohol intake could not account for the disparity in the incidence rates. Other work has suggested that environmental factors such as exposure to pesticides and solvents or genetic factors such as translocations involving Chromosomes 13 and 14 may play a role [9,10].There have been many reports of the familial occurrence of myeloma in the literature, implying a hereditary element or a common environmental factor [11][12][13][14][15][16]. Most of these families have been of Caucasian origin.…”

Anticipation in familial plasma cell dyscrasias

“…Our review of the literature reveals approximately 75 reports of familial myeloma. Although most reported familial cases involve siblings, myeloma in multiple generations of the same family has also been reported ( Goldstone et al , 1973 ; Zawadzki et al , 1977 ; Shoenfeld et al , 1982 ; Nadeau et al , 1956 ; Hubert et al , 1985 ; Meijers & Voormolen‐Kalova, 1972; Boga et al , 1973 ; Berlin et al , 1968 ; Manigand et al , 1970 ; McCrea & Morris, 1986; Rostoker et al , 1986 ; Crozes‐Bony et al , 1995 ; Blattner et al , 1980 ). In this paper we report six previously unpublished parent–child pairs with familial plasma cell dyscrasia, review 20 such pairs found in the literature, and demonstrate evidence for anticipation in familial plasma cell dyscrasia.…”