Animal model of human disease. Infantile X-linked agammaglobulinemia. Agammaglobulinemia in horses.

This research explores X-linked agammaglobulinemia in horses, a severe immune deficiency found in various horse breeds, leading to clinical signs like pneumonia and arthritis. Lymphoid tissues show an absence of B lymphocytes and low immunoglobulin levels, potentially contributing to the fatal course.

Introduction of the Disease

• X-linked agammaglobulinemia is a severe immune deficiency observed generally in male horses of thoroughbred, standardbred, and quarter horse breeds. The disease emerges 2-6 months after birth following the metabolism and elimination of immunoglobulins (antibodies) inherited from the mother.
• Clinical manifestations of the immune deficiency include pneumonia, enteritis (inflammation of the intestine), dermatitis (skin inflammation), arthritis (joint inflammation), and laminitis (hoof disease). The prognosis of this condition is typically grim, with death occurring at any time from 2-18 months of age.

Immune and Biological Features

• Immunologic evaluations in these horses show an absence of B lymphocytes (a type of white blood cell responsible for producing antibodies) and very low concentrations of various types of immunoglobulins (IgM, IgA, IgG and IgG(T)).
• Because of this deficiency, afflicted horses do not produce detectable antibodies after immunization. Interestingly, the number of T-lymphocytes (another type of white blood cell involved in immune responses) is normal, and these cells respond adequately when tested with immune challenges.
• Besides, normal adenosine deaminase activity was reported in the peripheral blood lymphocytes of one tested horse suffering from agammaglobulinemia.

Diagnosis of Agammaglobulinemia

• Upon histologic examination, lymphoid tissues demonstrate an absence of lymphoid follicles and plasma cells in lymph nodes and spleen.
• Also, noteworthy is the absence of the connective tissue stromal framework of lymphoid follicles, which are always seen in non-deficient horses. This only occurs in another severe immunodeficiency disorder of horses known as combined immunodeficiency.
• The diagnosis of agammaglobulinemia hinges on a normal lymphocyte count, absence of B lymphocytes, and low or undetectable concentrations of IgM, IgA, IgG(T), and IgG, all in the presence of normal T-lymphocyte responses. These criteria also help distinguish agammaglobulinemic horses from those with other similar disorders like combined immunodeficiency or selective IgM deficiency.