Cause

The cause of NHL is unknown, but the disease is usually associated with over-active B-lymphocytes and immune deficiency. B-cells are blood cells of the immune system produced in the bone marrow and the spleen, and they are involved in the production of antibodies.

Indicators of B-cell stimulation, high levels of immunoglobulin and p24 antigen in the blood, are apparent for several years before the emergence of NHL.

No-one knows exactly why the B-cells become over-activated. Possible causes include:

• HIV-related damage to the germinal centres in the lymph nodes where, in the healthy immune system, B-cells are normally exposed to foreign organisms.

• HIV-related disruption to normal levels of cytokines (chemical messengers).

• Repeated stimulation by organisms such as viruses.

The most common virus to cause this kind of problem is thought to be Epstein-Barr virus (EBV), which can be isolated from a high proportion of lymphomas. EBV is a common virus which has infected most people by adult life. On infection it may cause glandular fever, but afterwards it stays dormant in cells. EBV is particularly associated with the immunoblastic plasmacytoid subtype and may directly contribute to B-cell proliferation. Whether EBV plays a role in the development of Burkitt's lymphoma is more controversial.

NHL is more common among people who had Kaposi's sarcoma at their time of AIDS diagnosis than in people with other AIDS-defining infections such as Pneumocystis pneumonia (PCP). The link between the two conditions is unclear. However, it is clear that people with AIDS-related NHL are at increased risk of KS, and vice versa. Human herpes virus 8 (HHV-8), the virus linked to Kaposi's sarcoma, has been demonstrated to be present in the cells of one rare type of AIDS-related lymphoma, known as body-cavity based lymphoma.

A person's genetic make-up also influences his or her risk of NHL. The genetic variation known as SDF1-3'A is strongly associated with development of NHL in HIV-infected people. This genetic variation is more common among people of white European origin compared to those of black African origin.