Autoimmune vs. Autoinflammatory

A century ago Paul Ehrlich proposed that immune reactivity against self, which he called “horror autotoxicus” and which is now called autoimmunity, would be incompatible with life because of potentially devastating consequences for the host. But Ehrlich was proven wrong after the demonstration of autoantibodies and the emergence of a theoretical basis for autoreactivity. Conceptually, autoimmunity is viewed as a defect of either B or T lymphocyte selection, with aberrant lymphocytic responses to autoantigens. In recent years, an improved genetic understanding of both common and rare diseases, collectively associated with mutations reflecting immune system perturbations—ranging from the thymus, to B and T cells, to T regulatory cells—has vindicated the autoimmunity paradigm.

Nevertheless, there are several difficulties with the autoimmunity concept when considering self-directed tissue inflammation. These difficulties include a lack of major histocompatibility complex (MHC) and autoantibody associations in many diseases, tentatively labelled as autoimmune. A gradual appreciation of these difficulties has led to revised definitions of autoimmunity, but this approach fails to define when self-directed tissue inflammation is not autoimmune in origin.


And there is yet another weakness in the concept of autoimmunity: the idea that the immune system functions by making a distinction between self and nonself has come under scrutiny for failing to explain a number of findings. For example, “Why do we fail to reject tumors, even when many clearly express new or mutated proteins? Why do most of us harbor autoreactive lymphocytes without any sign of autoimmune disease, while a few individuals succumb?”.

To answer these questions, Polly Matzinger proposed the “danger signal theory,” which proposes that the immune system is not so much concerned with self/nonself discrimination but with mounting responses to danger signals, including exogenous pathogenic bacteria and endogenous damaged tissues. However, the danger model does not account adequately for the exquisite specificity of the adaptive immune responses in autoimmune diseases. This article draws on recent advances from genetic and molecular studies and improved clinical insights into disease in order to propose a unified classification and theoretical framework for all immunological diseases.

From: McGonagle D, McDermott MF (2006) A Proposed Classification of the Immunological Diseases. PLoS Med 3(8): e297. doi:10.1371/journal.pmed.0030297

Connective Tissue Disease

The ANA is positive. So is it Lupus, SLE, mixed connective tissue disease, or just a normal variant!? Dr. Davila helps us answer some of these questions with an excellent breakdown of auto-antibodies and connective tissue diseases.

(Note that the slide presentation is not viewable in email format – must visit the actual blog website to access the information).