Rabbit Anti-Human CD40 polyclonal antibody

Traditionally, primary immune deficiencies have been defined based on increased susceptibility to recurrent and/or severe infections. However, immune dysregulation, manifesting with autoimmunity or hyperinflammatory disease, has emerged as a common feature. This is especially true in patients affected by combined immune deficiency (CID), a group of disorders caused by genetic defects that impair, but do not completely abolish, T-cell function. Hypomorphic mutations in the recombination activating genes RAG1 and RAG2 represent the prototype of the broad spectrum of clinical and immunological phenotypes associated with CID. The study of patients with RAG deficiency and with other forms of CID has revealed distinct abnormalities in central and peripheral T- and B-cell tolerance as the key mechanisms involved in immune dysregulation. Understanding the pathophysiology of autoimmunity and hyperinflammation in these disorders may also permit more targeted therapeutic interventions.

B cell depletion via anti-CD20 antibodies is a highly effective treatment for multiple sclerosis (MS). However, little is known about the maturation/activation stage of the returning B cell population after treatment cessation and the wider effects on other immune cells. In the present study, 15 relapsing-remitting MS patients receiving 1,000 mg of rituximab were included. B, T, and myeloid cells were analyzed before anti-CD20 administration and in different time intervals thereafter over a period of 24 mo. In comparison to the phenotype before anti-CD20 treatment, the reappearing B cell pool revealed a less mature and more activated phenotype: 1) reappearing B cells were significantly enriched in transitional (before: 10.1 +/- 1.9%, after: 58.8 +/- 5.2%) and mature naive phenotypes (before: 45.5 +/- 3.1%, after: 25.1 +/- 3.5%); 2) the frequency of memory B cells was reduced (before: 36.7 +/- 3.1%, after: 8.9 +/- 1.7%); and 3) reappearing B cells showed an enhanced expression of activation markers CD25 (before: 2.1 +/- 0.4%, after: 9.3 +/- 2.1%) and CD69 (before: 5.9 +/- 1.0%, after: 21.4 +/- 3.0%), and expressed significantly higher levels of costimulatory CD40 and CD86. T cells showed 1) a persistent increase in naive (CD4(+): before: 11.8 +/- 1.3%, after: 18.4 +/- 3.4%; CD8(+): before: 12.5 +/- 1.4%, after: 16.5 +/- 2.3%) and 2) a decrease in terminally differentiated subsets (CD4(+): before: 47.3 +/- 3.2%, after: 34.4 +/- 3.7%; CD8(+): before: 53.7 +/- 2.1%, after: 49.1 +/- 2.7%).