b cell lymphoma | Hypocomplementemie C4 and diffuse lymphoma has large B cells: direct guilty or innocent bystander?

Hypocomplementemie C4 and diffuse lymphoma has large B cells: direct guilty or innocent bystander?




Introduction
The add-in is a major component of innate immunity. The C4 complement protein belongs to the classic route. Deficits in this way, hereditary or acquired protein are associated with deposits of immune complex diseases and predispose them to infection with encapsulated germs. If partial deficits in C4 are frequent in the general population and not necessarily associated with the development of autoimmune diseases, the complete lack of C4 is exceptional and joins a discoid lupus in the 75-87% of the cases.

Observation
A 44-year-old patient is addressed in our service because of the emergence of a generalized Lymphadenopathy, fatigue, weight loss and night sudations. The patient has no history or Comorbidities. The family history is negative for any inflammatory or tumoral pathology. Physical examination highlights the multiple painless Lymphadenopathy in lymph node areas level cervical and inguinal; the rest of the exam is normal. The biological balance is normal. Serologies viral HIV, HAV, HBV, HCV, EBV, CMV, parvovirus B19 are negative. The blood protein electrophoresis is normal as well as the weight dosage of immunoglobulins and IgG subclasses. The research of anti-nuclear antibodies (ACHAN) and anti-cytoplasme of the polymorphonuclear (ANCA) is negative. On the other hand, the total haemolytic complement (CH50) activity is dramatically lowered (1%; range 70-130%), associated with an activity of the C1 Inhibitor (78%; range (67-150%) and rates of C3 (1,20 g/L; range 0.66 - 1.35 g/L) normal, but with a deficit deep in) C4 (< 0.02 g/L; range 0.08 - 0.34 g/L). There is no of cryoglobulinemia. a mixture test shows an increase in the rate of C4 suggesting the absence of a neutralizing factor. The rate of antibodies against diphtheria, tetanus, measles, chicken pox and pathogens encapsulated streptococcus pneumoniae (serotypes 9 N, 11A, 14, 17F, 19, 23F), haemophilus influenzae type B and Neisseria meningitidis are normal. Analysis by flow cytometry in flow shows the presence of a monoclonal population of CD5 B cells-/ CD10-, suggesting a large low-grade B cell lymphoma. A PET - CT shows several best abdominal and cervical hypermetabolic adenomegalies and inhomogeneous fixated on humeral and femoral level 18 - FDG. A resection of a right paratracheale ganglion Thoracoscopic biopsy shows infiltration polyposis of B cells. The immunophenotyping reveals a monoclonal population B CD19 + / ++ CD20 / CD5-/ CD10/CD38/CD11c + / CD103/CD25/Ki67 + / + CD44 / BCL6dim / BCL2-/ IRF4 +. The puncture biopsy of spinal shows a nodular and interstitial infiltration by the lymphoma cells B lambda +, CD20 +, CD19 +, CD38-, CD5-. We retain a diagnosis of lymphoma B diffuse large cell with a phenotype of cells B activated stage IV according to classification of Hans and al, [1] with an international prognosis index (IPI) score of 2. After 6 cycles of chemotherapy by R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, sulfate vincristine, prednisone), the patient is in complete remission. Four weeks after the last chemotherapy treatment the CH50 and C4 rate is are quasi-normalisee (69% and 0.06 g/L respectively).

Conclusion
Here, we describe the case of a patient with no immunological past and develops a non-Hodgkin Lymphoma associated with a C4 complete deficit, which normalizes after Lymphoma treatment. The association of a C4 hypocomplementemie to lymphoma is described that during the association to a syndrome of Sjögren pre-existing [2]. The C4 of the complement protein is involved in the negative selection of auto-reactives B cells. Its deficit is therefore associated with prolonged survival of B cells with an increased risk of developing adverse mutations that can eventually lead to tumor development [3]. In our patient, the role of promoter of the deficit in C4 in the appearance of lymphoma is central, making him a "direct guilty". The routine exploration of the complement in patients with lymphomas could corroborate this hypothesis.