Primary immune regulatory disorders (PIRD) are characterized by a disturbance of immune tolerance and excessive inflammation.

IPEX is an X-linked disorder in which affected boys develop severe autoimmunity that can target any organ. The gut, skin, and endocrine organs—particularly the pancreas and thyroid gland—are the most common targets.

Innate immune disorders include Myd88 and IRAK-4 deficiencies, TLR3 deficiency, NF-kappa-B essential modulator (NEMO) deficiency syndrome, natural killer (NK) cell deficiency, and disorders in interferon-γ (IFN-γ) and interleukin (IL)-12/23 signaling pathways. 

Variants in the genes encoding cytotoxic T lymphocytic antigen-4 (CTLA4) and lipopolysaccharide responsive beige-like anchor (LRBA) can cause immune dysregulation. This means the components of the immune system regulating inflammation, autoimmunity, and cancer lose their proper function, leading to an array of autoimmune disorders and infections.

ALPS is a rare genetic disorder in which lymphocytes, a type of white blood cell, increase and accumulate in the spleen and lymph nodes. This is due to the failure of the mechanism that normally causes lymphocytes to die naturally.

Combined immune deficiencies (CID) are a group of primary immunodeficiencies in which both T cells and B cells of the adaptive immune system are either low or function poorly.

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder that causes neurological symptoms (like unsteady gait), dilated corkscrew-shaped blood vessels in the white of the eyes and on sun-exposed skin, combined immune deficiency, and high risk of cancer.