γ Heavy chain disease screening showing a discrepancy between electrophoretic and nephelometric determinations of serum γ globulin concentration

Abstract

A 75-year-old woman with rheumatoid arthritis showed a discrepancy between the reduced level of serum gamma globulin on cellulose acetate electrophoresis and the normal level of serum IgG determined by laser nephelometry. Although no M-peak was detectable on cellulose acetate electrophoresis, immunoelectrophoresis of the patient's serum revealed a monoclonal protein reacting with anti-IgG antiserum but not with anti-kappa or anti-lambda light chain antiserum. Western blotting of the patient's serum showed abnormal low-molecular-weight gamma chains. Thus, the patient was diagnosed with gamma heavy chain disease. A comparison of gamma globulin levels determined by different methods may be useful when screening for this disease.

Gamma heavy chain disease (γ-HCD) as iatrogenic immunodeficiency- associated lymphoproliferative disorder: Possible emergent subtype of rheumatoid arthritis-associated γ-HCD

“…To the best of our knowledge, 15 γ-HCD patients with RA as an underlying disease have been reported. 3,[6][7][8]10,11,[13][14][15][16][17][18][19][20] Two γ-HCD patients were treated using MTX and corticosteroid 10 or MTX alone 11 for RA before the onset of LPD, and were later found to have γ-HCD; therefore, γ-HCD in these 2 patients is considered to be iatrogenic immunodeficiency-associated LPD, because this LPD subtype is tentatively defined as that arising in patients with autoimmune diseases with a history of treatment with immunosuppressive agents such as MTX, 9 although the causative mechanism of MTX for the development of LPD has not been elucidated. One more γ-HCD patient had been treated using MTX for seronegative RA; however, the patient did not have constitutive symptoms, lymph node swelling, hepatosplenomegaly, tumoral lesions, or bone marrow abnormality at the time of γ-HCD diagnosis.…”

“…Therefore, γ-HCD in this patient lacked the clinical features of LPD and the diagnosis of iatrogenic immunodeficiency-associated LPD was unlikely. In the remaining 12 γ-HCD patients with RA, MTX or immunosuppressants were not used for RA treatment, 3,[6][7][8][13][14][15][16][17][18][19] although the treatment agent was not described for one patient. 7 Therefore, the present case may be the third reported case of γ-HCD as iatrogenic immunodeficiency-associated LPD.…”