A proposed classification of the immunological diseases

Abstract

The formal recognition and genetic understanding of the autoinflammatory diseases has defined mechanisms of self-directed inflammation that are independent of adaptive immunity.

Figure 1. The Immunological Disease Continuum, with Examples

The monogenic “autoinflammatory” diseases may be exclusively determined by local tissue-specific factors. For rare monogenic “autoimmune” conditions, the disease localisation appears to be determined predominantly by the adaptive immune response. The clinical heterogeneity within the immunological diseases, both among patients and between populations, may reflect the variable expression of autoinflammatory and autoimmune factors in disease causation. For example, in humans, there is considerable genetic and molecular evidence for uveitis falling into all of the disease categories, with the exception of the rare monogenic autoimmune diseases. There is also considerable overlap between polygenic autoinflammatory diseases and MHC class 1–associated diseases, but to simplify classification, these are split up into different categories. This figure does not include all immunologically recognised diseases because of their large number.

Figure 2. Recognition of Autoinflammation: Psoriatic Arthritis as an Example

In early RA, joint disease localisation is to the synovium—in keeping with the concept of the synovium being the primary target organ. However, in early psoriatic arthritis, the inflammatory changes have a widespread distribution and appear to relate to patterns of joint stressing around ligaments, adjacent bone, and soft tissues, rather than a specific antigen territory. The figure shows a contrast-enhanced high-resolution magnetic resonance image of a distal interphalangeal joint optimised for showing sites of inflammation (pixel size, 100 ×100 microns). There are extensive inflammatory changes in all tissues. Asterisk, site of diffuse osteitis; arrowhead, synovial enhancement; solid arrows, joint ligaments that show florid inflammatory changes at insertions and within ligaments; open arrow, extracapsular soft-tissue enhancement.