Historical background

In 1952 Colonel Ogden C Bruton reported the case of an 8-year-old boy with a 4 year history of recurrent bacterial sepsis, osteomyelitis and otitis. This child failed to make antibodies to pneumococcus after repeated antigenic challenge. In a seminal observation, Bruton noted that the patient's serum lacked the gamma globulin fraction by electrophor-etic analysis but was otherwise normal. This was the first case in which an abnormal result in a laboratory study explained the clinical problems and dictated the therapy for an immunodeficient patient. The patient was treated with gamma globulin and had a marked decrease in the incidence of infection. In the next 5 years many similar patients were reported.

Most of these patients could be divided into one of two groups. The first group consisted of adults who had the onset of recurrent or persistent infections after early childhood. Males and females appeared to be equally affected and the disorder could not be accounted for by a single gene defect by mendelian inheritance. This disorder came to be called acquired hypogammaglobulinemia or common variable immunodeficiency. The patients in the second group were boys who had the onset of their disease in the first 2 years of life. Many of these children had similarly affected brothers, maternal uncles or cousins. This disorder is now referred to as X-linked agammaglobulinemia (XLA), congenital agammaglobulinemia or Bruton's agammaglobulinemia.

Studies performed in the 1970s showed that patients with XLA had markedly reduced numbers of B cells in the peripheral circulation; however, pre-B cells could be found in their bone marrow, suggesting that stem cells could enter the B cell lineage but they could not progress through normal B cell differentiation. In 1986, preliminary linkage studies mapped the XLA defect to the midportion of the long arm of the X chromosome. The same year, X chromosome inactivation studies performed on the B cells of carriers of XLA, the mothers of affected boys, showed that the XLA gene product was expressed in B cells and it was not transportable between cells. In 1993, two groups, using positional cloning or analysis of a candidate gene, independently showed that XLA was due to mutations in the gene encoding a cytoplasmic tyrosine kinase which is now called Btk (Bruton tyrosine kinase) (Table 1).

How To Bolster Your Immune System

How To Bolster Your Immune System

All Natural Immune Boosters Proven To Fight Infection, Disease And More. Discover A Natural, Safe Effective Way To Boost Your Immune System Using Ingredients From Your Kitchen Cupboard. The only common sense, no holds barred guide to hit the market today no gimmicks, no pills, just old fashioned common sense remedies to cure colds, influenza, viral infections and more.

Get My Free Audio Book

Post a comment