Typically, diagnosis involves several preliminary tests of immune function, including basic evaluation of the humoral immune system and the cell-mediated immune system. A WBC differential will reveal extremely elevated levels of neutrophils (on the order of 6-10x normal) because they are unable to leave the blood vessels.

In the case of LAD-I, specific diagnosis is done by flow cytometry. This technique will reveal absent or reduced CD18 expression in the leukocyte membrane. Recently, prenatal diagnosis systems has been established, allowing an early detection of the disease.

LAD-II diagnosis includes the study of different glycosilated forms of the transferrin protein. In LAD-III, as platelet function is also affected, this could be used to differentiate it from the other types.

The diagnosis of hyper IgM syndrome can be done via the following methods and tests:

- MRI

- Chest radiography

- Pulmonary function test

- Lymph node test

- Laboratory test (to measure CD40)

The basic tests performed when an immunodeficiency is suspected should include a full blood count (including accurate lymphocyte and granulocyte counts) and immunoglobulin levels (the three most important types of antibodies: IgG, IgA and IgM).

Other tests are performed depending on the suspected disorder:

- Quantification of the different types of mononuclear cells in the blood (i.e. lymphocytes and monocytes): different groups of T lymphocytes (dependent on their cell surface markers, e.g. CD4+, CD8+, CD3+, TCRαβ and TCRγδ), groups of B lymphocytes (CD19, CD20, CD21 and Immunoglobulin), natural killer cells and monocytes (CD15+), as well as activation markers (HLA-DR, CD25, CD80 (B cells).

- Tests for T cell function: skin tests for delayed-type hypersensitivity, cell responses to mitogens and allogeneic cells, cytokine production by cells

- Tests for B cell function: antibodies to routine immunisations and commonly acquired infections, quantification of IgG subclasses

- Tests for phagocyte function: reduction of nitro blue tetrazolium chloride, assays of chemotaxis, bactericidal activity.

Due to the rarity of many primary immunodeficiencies, many of the above tests are highly specialised and tend to be performed in research laboratories.

Criteria for diagnosis were agreed in 1999. For instance, an antibody deficiency can be diagnosed in the presence of low immunoglobulins, recurrent infections and failure of the development of antibodies on exposure to antigens. The 1999 criteria also distinguish between "definitive", "probable" and "possible" in the diagnosis of primary immunodeficiency. "Definitive" diagnosis is made when it is likely that in 20 years, the patient has a >98% chance of the same diagnosis being made; this level of diagnosis is achievable with the detection of a genetic mutation or very specific circumstantial abnormalities. "Probable" diagnosis is made when no genetic diagnosis can be made, but the patient has all other characteristics of a particular disease; the chance of the same diagnosis being made 20 years later is estimated to be 85-97%. Finally, a "possible" diagnosis is made when the patient has only some of the characteristics of a disease are present, but not all.

Five "types" of hyper IgM syndrome have been characterized:

- Hyper-IgM syndrome type 1 (X-linked), characterized by mutations of the "CD40LG" gene. In this type, T cells cannot tell B cells to switch classes.

- Hyper-IgM syndrome type 2 (autosomal recessive), characterized by mutations of the "AICDA" gene. In this type, B cells cannot recombine genetic material to change heavy chain production

- Hyper-IgM syndrome type 3 characterized by mutations of the "CD40" gene. In this type, B cells cannot receive the signal from T cells to switch classes.

- Hyper-IgM syndrome type 4 which is a defect in class switch recombination downstream of the AICDA gene that does not impair Somatic Hypermutation.

- Hyper-IgM syndrome type 5 characterized by mutations of the "UNG" gene.

A 2009 study reported results from 36 children who had received a stem cell transplant. At the time of follow-up (median time 62 months), 75% of the children were still alive.

Health professionals must look at a person's history, symptoms, physical exam and laboratory test in order to make a diagnosis. If the results show patients with low levels of lymphocytes, absence of granulocytes or absence of thymus then the patient may be suspected to have RD.

The diagnosis of Nezelof syndrome will indicate a deficiency of T-cells, additionally in ascertaining the condition the following is done:

The differential diagnosis for this condition consists of acquired immune deficiency syndrome and severe combined immunodeficiency syndrome

The treatment of primary immunodeficiencies depends foremost on the nature of the abnormality. Somatic treatment of primarily genetic defects is in its infancy. Most treatment is therefore passive and palliative, and falls into two modalities: managing infections and boosting the immune system.

Reduction of exposure to pathogens may be recommended, and in many situations prophylactic antibiotics or antivirals may be advised.

In the case of humoral immune deficiency, immunoglobulin replacement therapy in the form of intravenous immunoglobulin (IVIG) or subcutaneous immunoglobulin (SCIG) may be available.

In cases of autoimmune disorders, immunosuppression therapies like corticosteroids may be prescribed.

The old diagnostic criteria for the illness included: Chronic non-malignant lymphoproliferation, elevated peripheral blood DNTs and defective in vitro Fas mediated apoptosis.

The new criteria require chronic non-malignant lymphoproliferation (over six months lymphadenopathy and/or splenomegaly), elevated peripheral blood DNTs. A primary accessory in diagnosis is defective in vitro Fas mediated apoptosis and somatic or germline mutation in ALPS causative gene (FAS, FASL, CASP10).

The secondary accessory in diagnosis are elevated biomarkers (plasma sFASL over 200 pg/ml, plasma IL-10 >20 pg/ml, plasma or serum vitamin B12 >1500 ng/L, Plasma IL-18 >500pg/ml) and immunohistochemical findings on biopsy consistent with ALPS as determined by an experienced hematopathologist. Another sign is autoimmune cytopenias and polyclonal hypergammaglobulinemia and a family history of ALPS or non-malignant lymphoproliferation.

A definitive diagnosis is chronic non-malignant lymphoproliferation and/or elevated peripheral blood DNTs plus one primary accessory criterion. A probable diagnosis is the same but with one secondary accessory criterion.

Though BLSII is an attractive candidate for gene therapy, bone marrow transplant is currently the only treatment.

Gene therapy is a relatively new concept in the field of SCID. This therapy is currently undergoing clinical trial and has cured a small number of children suffering from X-linked SCID and recessive allele SCID. Gene therapy aims to correct the underlying genetic abnormality in SCID. In the case of RD, the genetic abnormality would be AK2 malfunction. Stem cells are taken from an affected child's blood or bone marrow. Then in laboratory conditions the stem cells are manipulated and corrected with gene technology. They are then injected back into the patient. Similarly, in bone transplant, stem cells are able to find their way back through tracking mechanisms.

In terms of diagnosis for this condition, the following methods/tests are available:

- Endoscopic

- CT scan

- Serum endocrine autoantibody screen

- Histologic test

Treatment consists mainly of high dose antibiotics for active infections and prophylactic antibiotics for prevention of future infections. GM-CSF therapy or bone marrow transplant might be considered for severe cases. Prognosis is difficult to predict, but patients receiving treatment are generally able to survive to adulthood.

2003 nomenclature

- IA - Fas

- IB - Fas ligand

- IIA - Caspase 10

- IIB - Caspase 8

- III - unknown

- IV - Neuroblastoma RAS viral oncogene homolog

Revised nomenclature (2010)

- ALPS-FAS: Fas. Germline FAS mutations. 70% of patients. Autosomal dominant. Dominant negative and haploinsufficient mutations described.

- ALPS-sFAS: Fas. Somatic FAS mutations in DNT compartment. 10% of patients

- ALPS-FASL: Fas ligand. Germline FASL mutations. 3 reported cases

- ALPS-CASP10: Caspase 10. Germline CASP10 mutation. 2% of patients

- ALPS-U: Undefined. 20% of patients

- CEDS: Caspase 8 deficiency state. No longer considered a subtype of ALPS but distinct disorder

- RALD: NRAS, KRAS. Somatic mutations in NRAS and KRAS in lympocyte compartment. No longer considered a subtype of ALPS but distinct disesase

Available treatment falls into two modalities: treating infections and boosting the immune system.

Prevention of Pneumocystis pneumonia using trimethoprim/sulfamethoxazole is useful in those who are immunocompromised. In the early 1950s Immunoglobulin(Ig) was used by doctors to treat patients with primary immunodeficiency through intramuscular injection. Ig replacement therapy are infusions that can be either subcutaneous or intravenously administrated, resulting in higher Ig levels for about three to four weeks, although this varies with each patient.

Once a diagnosis is made, each individual's treatment is based on an individual’s clinical condition. Hematopoietic stem cell transplant is a possible treatment of this condition but its effectiveness is unproven.

Additionally, magnesium supplementation is a promising potential treatment for XMEN. One of the consequences of loss of "MAGT1" function is a decreased level of unbound intracellular Mg2+. This decrease leads to loss of expression of an immune cell receptor called "NKG2D", which is involved in EBV-immunity. Remarkably, Mg2+ supplementation can restore "NKG2D" expression and other functions that are abnormal in patients with XMEN. Early evidence suggests continuous oral magnesium threonate supplementation is safe and well tolerated. Nonetheless, further research is needed to evaluate the use of Mg2+ as a treatment for XMEN. It remains unclear if such supplementation will protect against the development of lymphoma in patients with XMEN. Investigators at the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health currently have clinical protocols to study new approaches to the diagnosis and treatment of this disorder.

Once a diagnosis is made, the treatment is based on an individual’s clinical condition and may include standard management for autoimmunity and immunodeficiency. Hematopoietic stem cell transplantation has cured the immune abnormalities in one TRIANGLE patient, although the neurodevelopmental delay would likely remain. Investigators at the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health currently have clinical protocols to study new approaches to the diagnosis and treatment of this disorder.

The cause of immunodeficiency varies depending on the nature of the disorder. The cause can be either genetic or acquired by malnutrition and poor sanitary conditions. Only for some genetic causes, the exact genes are known. Although there is no true discrimination to who this disease affects, the genes are passed from mother to child, and on occasion from father to child. Women tend not to show symptoms due to their second X chromosome not having the mutation while man are symptomatic, due to having one X chromosome.

Estimation of the frequency of SGD is difficult, as it is an extremely rare disease with few cases reported in literature. The condition was first reported in 1980, and since only a handful more cases have been published.

The bare lymphocyte syndrome, type II (BLS II) is a rare recessive genetic condition in which a group of genes called major histocompatibility complex class II (MHC class II) are not expressed.

The result is that the immune system is severely compromised and cannot effectively fight infection. Clinically, this is similar to severe combined immunodeficiency (SCID), in which lymphocyte precursor cells are improperly formed. As a notable contrast, however, bare lymphocyte syndrome does not result in decreased B- and T-cell counts, as the development of these cells is not impaired.

Diarrhea can be among the associated conditions.

The clinical symptoms are caused by abnormalities of the immune system and disruption of basic cellular functions. Patients show markedly decreased circulating T cells, B cells and natural killer (NK) cells, with severely reduced naive T cells and hypergammaglobulinemia.

Diagnosis of autoimmune disorders largely rests on accurate history and physical examination of the patient, and high index of suspicion against a backdrop of certain abnormalities in routine laboratory tests (example, elevated C-reactive protein). In several systemic disorders, serological assays which can detect specific autoantibodies can be employed. Localised disorders are best diagnosed by immunofluorescence of biopsy specimens. Autoantibodies are used to diagnose many autoimmune diseases. The levels of autoantibodies are measured to determine the progress of the disease.

An autoimmune disease is a condition arising from an abnormal immune response to a normal body part. There are at least 80 types of autoimmune diseases. Nearly any body part can be involved. Common symptoms include low grade fever and feeling tired. Often symptoms come and go.

An immune disorder is a dysfunction of the immune system. These disorders can be characterized in several different ways:

- By the component(s) of the immune system affected

- By whether the immune system is overactive or underactive

- By whether the condition is congenital or acquired

According to the International Union of Immunological Societies, more than 150 primary immunodeficiency diseases (PIDs) have been characterized. However, the number of acquired immunodeficiencies exceeds the number of PIDs.

It has been suggested that most people have at least one primary immunodeficiency. Due to redundancies in the immune system, though, many of these are never detected.