Human C1q Deficiency and Allogeneic Hematopoietic Stem Cell Transplantation

Human C1q deficiency is a rare disorder associated with systemic lupus erythematosus (SLE) and increased susceptibility to severe bacterial infections with mainly encapsulated organisms. Among patients with C1q deficiency there is a great variation in the severity of symptoms, however, the majority of patients requires comprehensive medical therapy and some develop treatment resistant disease. Since C1q is produced by monocytes it has been speculated that allogeneic hematopoietic stem cell transplantation (allo-HSCT) may cure these patients. At our center, we have so far treated five patients with C1q deficiency. In three cases, SLE symptoms remained relatively mild after the initiation of medical therapy, but two patients developed treatment resistant SLE and we decided to pursue with allo-HSCT. Here, we report an unrelated allo-HSCT in a 9-year-old boy who suffered from refractory SLE of the central nervous system and a related allo-HSCT in a 12-year-old girl with refractory SLE. Both patients restored C1q production post-transplant, and the severity of their SLE was attenuated. The boy developed post-transplant lymphoproliferative disease, which resolved after rituximab and donor lymphocyte infusions (DLI). Unfortunately, the DLIs induced cortisone-resistant severe gastrointestinal graft-versus-host disease, and he died from multiple organ failure four months post-transplant. The girl is doing well 21 months post-transplant, and clinically all signs of SLE have resolved. We believe that allo-HSCT is a promising treatment in patients with C1q deficiency and severe SLE, which needs further investigation.