Monoclonal IgG in MGUS and multiple myeloma targets infectious pathogens.

Subsets of mature B cell neoplasms are linked to infection with intracellular pathogens such as Epstein-Barr virus (EBV), hepatitis C virus (HCV), or Helicobacter pylori. However, the association between infection and the immunoglobulin-secreting (Ig-secreting) B proliferative disorders remains largely unresolved. We investigated whether the monoclonal IgG (mc IgG) produced by patients diagnosed with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM) targets infectious pathogens. Antigen specificity of purified mc IgG from a large patient cohort (n = 244) was determined using a multiplex infectious-antigen array (MIAA), which screens for reactivity to purified antigens or lysates from 9 pathogens. Purified mc IgG from 23.4% of patients (57 of 244) specifically recognized 1 pathogen in the MIAA. EBV was the most frequent target (15.6%), with 36 of 38 mc IgGs recognizing EBV nuclear antigen-1 (EBNA-1). MM patients with EBNA-1-specific mc IgG (14.0%) showed substantially greater bone marrow plasma cell infiltration and higher ß2-microglobulin and inflammation/infection-linked cytokine levels compared with other smoldering myeloma/MM patients. Five other pathogens were the targets of mc IgG: herpes virus simplex-1 (2.9%), varicella zoster virus (1.6%), cytomegalovirus (0.8%), hepatitis C virus (1.2%), and H. pylori (1.2%). We conclude that a dysregulated immune response to infection may underlie disease onset and/or progression of MGUS and MM for subsets of patients.

The role of Helicobacter pylori infection in hematological disorders.

Helicobacter pylori (H. pylori) is a Gram-negative spiral bacterium, classified as a carcinogen of class I, according to the World Health Organization (WHO). The infection is a major cause of gastritis, gastric and duodenal ulcer disease and increases the risk of gastric cancer. It has been implicated in the pathogenesis of several gastrointestinal, systemic or hematological diseases. The present review aims in deciphering the role of the bacterium in hematological disorders, increasing the awareness of gastroenterologists, hematologists and internal medicine practitioners, regarding the bacterium-associated hematological diseases. The efficacy of H. pylori eradication in increasing the platelet count in adult patients with primary immune thrombocytopenia (ITP) has been confirmed, linking the infection with the disease. Moreover, as the bacterium causes iron deficiency anemia (IDA) by several mechanisms, recent guidelines indicate H. pylori infection (Hp-I) to be sought in IDA patients if histology is negative and to be eradicated if present. Furthermore, it has been widely recognized that anti-H. pylori treatment causes regression of the low-grade B-cell gastric MALT lymphomas. Despite the well established associations of Hp-I with the aforementioned hematological disorders, we highlight the possible role of the infection to other hematological diseases or conditions such as non-Hodgkin lymphomas of the stomach, monoclonal gammopathy of undetermined significance, megaloblastic anemia and myelodysplastic syndromes. We finally underline the elevated risk of childhood leukemia and of hemorrhage in patients with coagulation disorders, due to the infection.

Monoclonal and biclonal gammopathy in two patients infected with Bartonella henselae.

Two immunocompetent patients with cat-scratch disease due to infection with Bartonella henselae developed monoclonal and biclonal gammopathy. Neither patient had evidence of any other known cause of plasma cell dyscrasia, and antibiotic eradication of Bartonella henselae infection resulted in the prompt disappearance of the gammopathy. Hence, cat-scratch disease should be added to the list of possible underlying disorders in individuals presenting with monoclonal and biclonal gammopathy.

[Epstein-Barr virus infection and immunoglobulin abnormalities in renal transplant recipients]. / Infezione da virus di Epstein-Barr ed anomalie immunoglobuliniche nei portatori di trapianto renale.

The relationship between immunoglobulin abnormalities and EBV infection has been investigated in 65 renal transplant patients. Immunoglobulins abnormalities were demonstrated in 44 (68%) patients, 8 of them (18%, 12% of all patients) had a monoclonal component. Up to now no lymphoproliferative disorder has been observed in these patients. All patients were EBV seropositive at the beginning of the study and in 22 of them (33%) a reactivation of EBV infection could be demonstrated. No relation has been observed between immunoglobulin abnormalities, EBV reactivation, age or sex. By contrast, a significant relation was found between EBV reactivation and immunosuppressive treatment: patients under triple therapy with Azathioprine, Cyclosporine A and Prednisone had less EBV reactivation compared to those under Cyclosporine A treatment.