A patient with paroxysmal nocturnal hemoglobinuria, T cell large granular lymphocyte clonal expansion, and monoclonal gammopathy of undetermined significance

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH) has been described in association separately with T cell large granular lymphocyte (LGL) clonal expansions and plasma cell dyscrasias. We describe a patient with anemia related to hemolytic PNH, with concurrent T cell LGL oligoclonal expansion and IgG k monoclonal gammopathy of undetermined significance. Peripheral blood flow cytometry revealed decreased expression of CD55 and CD59 on erythrocytes and decreased expression of CD55 and CD66 on neutrophils. An LGL population was present in the peripheral blood and was characterized as oligoclonal by polymerase chain reaction-based analysis of the T cell receptor c-chain variable region. Serum protein electrophoresis with immunofixation showed a low level IgG k monoclonal protein.We describe the diagnostic evaluation of this patient and provide a brief review of the reported associations among PNH, LGL clonal expansion, and monoclonal gammopathy.

Hemorheological parameters in Monoclonal Gammopathy of Undetermined Significance (MGUS)

“…The only abnormality of the erythrocyte membrane noted in MGUS regards the membrane proteins and consists in the presence of a paroxysmal nocturnal hemoglobinuria-like (PNH-like) defect in some MGUS subjects [12,33]. This defect is characterized by an altered synthesis of glycosilphosphatidylinositol, which is essential for the binding of some surface proteins, such as CD55 and CD59, able to protect the red blood cells from intravascular lysis.…”

Persistent Large Granular Lymphocyte Clonal Expansions: “The Root of Many Evils”—And of Some Goodness

“…Other cases have shown oligoclonal or non-clonal LGL expansions associated with PNH. In 2006, Fukumoto and Gotlib reported a PNH patient with oligoclonal T-LGL expansion, accompanied by a monoclonal IgG-lambda gammopathy of undetermined significance [ 129 ]. Boyer et al communicated the case of a concomitant PNH-T-LGL disease, confirmed by immunophenotypic analysis (CD3+ CD8+ CD56+ CD16+) and BM biopsy (interstitial infiltration of CD8+ T lymphocytes, with overexpression of TIA-1).…”

Paroxysmal nocturnal hemoglobinuria may cause retinal vascular occlusions

“…Using flow cytometry analysis for CD55 and CD59, as the established method of detection [6,7], the correct diagnosis of PNH could be made. This assay utilizes antibodies directed against GPI-AP to identify populations of GPI-AP-deficient peripheral red blood cells, and both determines the percentage of cells that are abnormal and identifies discrete populations with different degrees of deficiency, thereby providing essential information in managing the anaemia of PNH.…”