The immune system is designed to recognize pathogenic invaders and elicit specific and appropriate immunological responses. When the immune system fails to distinguish self from nonself and elicits responses that are typically meant for defending the host from antigens, autoimmune disorders ensue. Several preventative mechanisms exist to prevent autoimmunity and to build immunological tolerance for the self molecules. Autoimmunity results when there is a breach of immunological tolerance. Autoimmune disorders could be confined to specific organs (rheumatoid arthritis (RA)) or could be systemic (systemic lupus erythematosus (SLE)). Approximately 100 distinct autoimmune disorders have been described, with the most common being type 1 diabetes (T1D), RA, SLE, inflammatory bowel diseases (IBD) and multiple sclerosis (MS).1
What is breach of immunological tolerance?
Immune tolerance is the ability conferred by the immune system against targeting self molecules, cells or tissues. In healthy individuals, lymphocytes with a propensity to attack self molecules are negatively selected and removed in the thymus (central tolerance). After exiting the thymus, mature T cells are selected again by a mechanism called peripheral tolerance, through which most of the self-reacting T cells are deleted. In the event that B cells express antibodies against self surface antigens are eliminated through clonal deletion. In addition, T regulatory cells (Tregs) help maintain peripheral immune tolerance. Even under this strict control, some autoreactive T and B cells leak into the periphery. While in most cases they are harmless (physiological autoimmunity), they could cause severe dysregulation of both innate and adaptive immunity, resulting in tissue damage (pathological autoimmunity).1
Targets and immune monitoring of different autoimmune disorders
As the targets of different autoimmune disorders vary, each disorder is characterized by a unique response.
Type 1 diabetes
In type 1 diabetes (T1D), the immune system attacks beta cells, the insulin producing cells in the pancreas. Several immune biomarkers have been associated with T1D such as HLA genotypes and autoantibodies, but most of them are not discriminative of the condition. As T cells are the immune components targeting pancreatic beta cells for destruction, analyzing autoantibodies in combination with T and B cell profiles provide more insight on disease signatures and help in monitoring disease evolution and response to treatment.2
Rheumatoid arthritis
In rheumatoid arthritis (RA), the synovium membrane that surrounds the joints are targeted by immune cells, which induces swelling, pain and inflammation. This chronic inflammatory response thickens the synovium, causing stiffness, limits proper motion of the joint and can progressively deform the joint and destroy its cartilage and bone. Presence of anticitrullinated antibodies prior to the onset of the disease and the presence of rheumatoid factors (RF) are hallmarks of RA and present in most RA cases. Myeloid cells, in particular macrophages, B cell lineages and cytokine profiles can be detected in the synovium at different stages of the disease.3,4 Proinflammatory cytokines such as tumor necrosis factor (TNF) play a role in RA pathogenesis. Using anti-TNF receptors can help make TNF biologically inactive and reduce its inflammatory activity.5
Systemic lupus erythematosus
Systematic lupus erythematosus (SLE) is the autoimmune disease with the most alterations in B cell homeostasis.4 An initial observation in SLE is B cell lymphopenia with decreased absolute numbers of both CD27+ and CD27− B cells as well as decreased proportions of IgD+CD27+ memory B cells. Regardless of disease activity or state, the loss of UM B cells is found in almost all SLE patients. Therefore, when combined with other informative clinical parameters such as positivity for antinuclear antibodies (ANA), B cell profiling can help identify potential biomarkers relevant to lupus disease.4,6
Multiple sclerosis
Multiple sclerosis (MS) is a demyelinating autoimmune disease that leads to central nervous system (CNS) impairments. MS is associated with peculiar cytokine signature profiles. Cell surface markers such as CD74 (MHC class II invariant chain) can be monitored by flow cytometry not only to assess disease activity and progression, but also to evaluate the clinical efficacy of treatment.7 Other markers such as percentages of blood CD19+CD5+ B cells and CD8+perforin+ T lymphocytes can also predict response to interferon-beta in relapsing-remitting multiple sclerosis patients.8 In addition, CD19 and CD20 counts are also used as markers for clinicians to evaluate treatment efficacy of rituximab, a monoclonal antibody directed at CD20+ B cells.9
