Treatment of systemic lupus erythematosus in two patients with extreme B-cell lymphopenia: importance of immunomonitoring and avoidance of B-cell targeted therapy.
BACKGROUND
Because dysfunction of the B-cell compartment is thought to be important in the pathogenesis of systemic lupus erythematosus (SLE), there has been a recent focus on therapies that target humoral immunity via multiple mechanisms. The aim of this paper was to demonstrate the importance of immunomonitoring in two cases with class II lupus nephritis on steroids who presented with a flare-up of disease. After a thorough work-up for infectious triggers of disease activity, conversion to another histopathological class of lupus nephritis was suspected. Deterioration of the patients' clinical condition made kidney biopsy impossible, and as B-cell targeted therapy was considered, we decided to perform an immunophenotypic analysis and to tailor therapy to the results of the lymphocyte profile. As we incidentally found extremely low B-cell counts, any B-cell-targeted therapy was prohibited, and cyclophosphamide (Cy) was considered a viable therapeutic option.


METHODS
We performed flow-cytometric lymphocyte (Ly) phenotyping (CD19, CD3, CD3CD4, CD3CD8, CD56/16) on two patients with class II lupus nephritis before and after two intravenous (i.v.) Cy pulse administrations. During all this time, patients were on steroids.


RESULTS
Both patients showed extreme B-cell lymphopenia, a marker of active SLE, which was not greatly impacted by the treatment over the follow-up period.


CONCLUSIONS
As current therapies are aimed at targeting the B cell, an important component of adaptive immunity, caution must be exercised before their use. In addition, monitoring of Ly subsets is essential due to the occurrence of extreme B-cell lymphopenia.
Division of Nephrology, University of Medicine and Pharmacy V. Babes Timisoara, Romania. gluh@umft.ro
Cristina
C
Gluhovschi
Gheorghe
G
Gluhovschi
Diana
D
Herman
Virginia
V
Trandafirescu
Ligia
L
Petrica
Silvia
S
Velciov
Gheorghe
G
Bozdog
Flaviu
F
Bob
Daniel
D
Cioca
D000328:Adult; D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology*; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D003520:Cyclophosphamide / Q000494:pharmacology / Q000627:therapeutic use; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000150:complications* / Q000188:drug therapy* / Q000628:therapy; D008181:Lupus Nephritis / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000628:therapy; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000473:pathology; D008231:Lymphopenia / Q000209:etiology* / Q000473:pathology*; D015166:Monitoring, Immunologic / Q000379:methods*; D011241:Prednisone / Q000627:therapeutic use; D011507:Proteinuria / Q000209:etiology / Q000652:urine; D006435:Renal Dialysis; D016896:Treatment Outcome; D055815:Young Adult
D003520:Cyclophosphamide; D003404:Creatinine; D011241:Prednisone