The diagnosis of T cell deficiency can be ascertained in those individuals with this condition via the following:

- Delayed hypersensitivity skin test

- T cell count

- Detection via culture(infection)

Complete or partial deficiency

- "Complete insufficiency" of T cell function can result from hereditary conditions (also called primary conditions) such as severe combined immunodeficiency (SCID), Omenn syndrome, and cartilage–hair hypoplasia.

- "Partial insufficiencies" of T cell function include acquired immune deficiency syndrome (AIDS), and hereditary conditions such as DiGeorge syndrome (DGS), chromosomal breakage syndromes (CBSs), and B-cell and T-cell combined disorders such as ataxia-telangiectasia (AT) and Wiskott–Aldrich syndrome (WAS).

- "Primary (or hereditary) immunodeficiencies" of T cells include some that cause complete insufficiency of T cells, such as severe combined immunodeficiency (SCID), Omenn syndrome, and Cartilage–hair hypoplasia.

- "Secondary causes" are more common than primary ones. Secondary (or acquired) causes are mainly:

Flow cytometry with monoclonal antibodies is used to screen for deficiencies of CD18.

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.

Among the diagnostic tests that can be done in determining if an individual has complement deficiencies is:

- CH50 measurement

- Immunochemical methods/test

- C3 deficiency screening

- Mannose-binding lectin (lab study)

- Plasma levels/regulatory proteins (lab study)

The only treatment for Omenn syndrome is chemotherapy followed by a bone marrow transplantation. Without treatment, it is rapidly fatal in infancy.

Patients show markedly low immunoglobulin levels of IgG, IgA, and IgM.

Because the CD18 gene has been cloned and sequenced, this disorder is a potential candidate for gene therapy.

Once a diagnosis is made, the treatment is based on an individual’s clinical condition. Based on the apparent activation of the mTOR pathway, Lucas and colleagues treated patients with rapamycin, an mTOR inhibitor. This effectively reduced hepatosplenomegaly and lymphadenopathy, most likely by restoring the normal balance of naïve, effector, and memory cells in the patients’ immune system. More research is needed to determine the most effective timing and dosage of this medication and to investigate other treatment options. 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.

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.

Those affected with deficiency of the interleukin-1–receptor antagonist can have diagnosis achieved via noting an increase of erythrocyte sedimentation rate, as well as the following:

- Genetic test

- Radiological findings

- Clinical findings

In terms of management for complement deficiency, immunosuppressive therapy should be used depending on the disease presented. A C1-INH concentrate can be used for angio-oedema (C1-INH deficiency).

Pneumococcus and haemophilus infections prevention can be taken via immunization for those with complement deficiency. Epsilon-aminocaproic acid could be used to treat hereditary C1-INH deficiency, though the possible side effect of intravascular thrombosis should be weighed.

The symptoms are very similar to graft-versus-host disease (GVHD). This is because the patients have some T cells with limited levels of recombination with the mutant RAG genes. These T cells are abnormal and have a very specific affinity for self antigens found in the thymus and in the periphery. Therefore, these T cells are auto-reactive and cause the GVHD phenotype.

A characteristic symptom is chronic inflammation of the skin, which appears as a red rash (early onset erythroderma). Other symptoms include eosinophilia, failure to thrive, swollen lymph nodes, swollen spleen, diarrhea, enlarged liver, low immunoglobulin levels (except immunoglobulin E, which is elevated), low T cell levels, and no B cells.

The clinical symptoms are caused by immunological abnormalities (figure 2). These include deficiency in CD27+ B memory cells, overrepresentation of CD10+ transitional B cells, expanded effector (CCR7-) T cells, expanded CD57+ senescent CD8+ T cells, and alterations in serum immunoglobulin concentrations, most with normal to elevated concentrations of IgM and reduced concentrations of IgA.

A new investigation has identified a seemingly successful treatment for LRBA deficiency by targeting CTLA4. Abatacept, an approved drug for rheumatoid arthritis, mimics the function of CTLA4 and has found to reverse life-threatening symptoms. The study included nine patients that exhibited improved clinical status and halted inflammatory conditions with minimal infectious or autoimmune complications. The study also suggests that therapies like chloroquine or hydroxychloroquine, which inhibit lysosomal degradation, may prove to be effective, as well. Larger cohorts are required to further validate these therapeutic approaches as effective long-term treatments for this disorder.

Gleich's syndrome, which may be a form of lymphocyte-variant hypereosinophilia, involves hypereosinophilia, elevated blood levels of IgM antibodies, and clonal expansion of T cells. Similar to lymphocyte=variant hypereosinophilia, the increased levels of blood eosinophils in Gleich's syndrome is thought to be secondary to the secretion of eosinophil-stimulating cytokines by a T cell clone(s).

In terms of treatment a 2013 review indicates that colchicine can be used for DIRA. Additionally there are several other management options such as anakinra, which blocks naturally occurring IL-1, this according to a 2016 pediatric textbook.

Familial eosinophilia is a rare congenital disorder characterized by the presence of sustained elevations in blood eosinophil levels that reach ranges diagnostic of eosinophilia or, far more commonly, hypereosinophilia. It is an autosomal dominant disorder in which genetic linkage gene mapping family studies localize the gene responsible for it to chromosome 5 at position q31-q33, between markers D5S642 and D5S816. This region contains a cytokine gene cluster which includes three genes whose protein products function in regulating the development and proliferation of eosinophils viz., interleukin 3, interleukin 5, and colony stimulating factor 2. However, no functional sequence genetic polylmophisms are found within the promoter, exons, or introns, of these genes or within the common gene enhancer for interleukin 3 or colony stimulating factor 2. This suggests that the primary defect in familial eosinophilia is not a mutation in one of these genes but rather in another gene within this chromosome area. Clinical manifestations and tissue destruction related to the eosinophilia in this disorder are uncommon: familial eosinophilia typically has a benign phenotype compared to other congenital and acquired eosinophilic diseases.

Diagnosis is confirmed histologically by tissue biopsy. Hematoxylin-eosin stain of biopsy slide will show features of Langerhans Cell e.g. distinct cell margin, pink granular cytoplasm. Presence of Birbeck granules on electron microscopy and immuno-cytochemical features e. g. CD1 positivity are more specific. Initially routine blood tests e.g. full blood count, liver function test, U&Es, bone profile are done to determine disease extent and rule out other causes. Radiology will show osteolytic bone lesions and damage to the lung. The latter may be evident in chest X-rays with micronodular and interstitial infiltrate in the mid and lower zone of lung, with sparing of the Costophrenic angle or honeycomb appearance in older lesions. MRI and CT may show infiltration in sella turcica. Assessment of endocrine function and bonemarrow biopsy are also performed when indicated.

- S-100 protein is expressed in a cytoplasmic pattern

- peanut agglutinin (PNA) is expressed on the cell surface and perinuclearly

- major histocompatibility (MHC) class II is expressed (because histiocytes are macrophages)

- CD1a

- langerin (CD207), a Langerhans Cell–restricted protein that induces the formation of Birbeck granules and is constitutively associated with them, is a highly specific marker.

Neutrophils (also known as neutrocytes) are the most abundant type of granulocytes and the most abundant (40% to 70%) type of white blood cells in most mammals. They form an essential part of the innate immune system. Their functions vary in different animals.

They are formed from stem cells in the bone marrow. They are short-lived and highly motile, or mobile, as they can enter parts of tissue where other cells/molecules cannot. Neutrophils may be subdivided into segmented neutrophils and banded neutrophils (or bands). They form part of the polymorphonuclear cells family (PMNs) together with basophils and eosinophils.

The name "neutrophil" derives from staining characteristics on hematoxylin and eosin (H&E) histological or cytological preparations. Whereas basophilic white blood cells stain dark blue and eosinophilic white blood cells stain bright red, neutrophils stain a neutral pink. Normally, neutrophils contain a nucleus divided into 2–5 lobes.

Neutrophils are a type of phagocyte and are normally found in the bloodstream. During the beginning (acute) phase of inflammation, particularly as a result of bacterial infection, environmental exposure, and some cancers, neutrophils are one of the first-responders of inflammatory cells to migrate towards the site of inflammation. They migrate through the blood vessels, then through tissue, following chemical signals such as Interleukin-8 (IL-8), C5a, fMLP, Leukotriene B4 and HO in a process called chemotaxis. They are the predominant cells in pus, accounting for its whitish/yellowish appearance.

Neutrophils are recruited to the site of injury within minutes following trauma, and are the hallmark of acute inflammation; however, due to some pathogens being indigestible, they can be unable to resolve certain infections without the assistance of other types of immune cells.

Diagnosis

Originally NEMO deficiency syndrome was thought to be a combination of Ectodermal Dysplasia (ED) and a lack of immune function, but is now understood to be more complex disease. NEMO Deficiency Syndrome may manifest itself in the form of several different diseases dependent upon mutations of the IKBKG gene such as Incontinentia pigmenti or Ectodermal dysplasia.

The clinical presentation of NEMO deficiency is determined by three main symptoms:

1. Susceptibility to pyogenic infections in the form of severe local inflammation

2. Susceptibility to mycobacterial infection

3. Symptoms of Ectodermal Dysplasia

To determine whether or not patient has NEMO deficiency, an immunologic screen to test immune system response to antigen may be used although a genetic test is the only way to be certain as many individuals respond differently to the immunological tests.

Commonly Associated Diseases

NEMO deficiency syndrome may present itself as Incontinentia pigmenti or Ectodermal dysplasia depending on the type of genetic mutation present, such as if the mutation results in the complete loss of gene function or a point mutation.

Amorphic genetic mutations in the IKBKG gene, which result in the loss of gene function, typically present themselves as Incontinetia Pigmenti (IP). Because loss of NEMO function is lethal, only heterozygous females or males with XXY karyotype or mosaicism for this gene survive and exhibit symptoms of Incontinetia Pigmenti, such as skin lesions and abnormalities in hair, teeth, and nails. There are a variety of mutations that may cause the symptoms of IP, however, they all involve the deletion of exons on the IKBKG gene.

Hypomorphic genetic mutations in the IKBKG gene, resulting in a partial loss of gene function, cause the onset of Anhidrotic ectodermal dysplasia with Immunodeficiency (EDA-IP). The lack of NEMO results in a decreased levels of NF-κB transcription factor translocation and gene transcription, which in turn leads to a low level of immunoglobulin production. Because NF-κB translocation is unable to occur without proper NEMO function, the cell signaling response to immune mediators such as IL-1β, IL-18, and LPS are ineffective thus leading to a compromised immune response to various forms of bacterial infections.

Treatment

The aim of treatment is to prevent infections so children will usually be started on immunoglobulin treatment. Immunoglobulin is also known as IgG or antibody. It is a blood product and is given as replacement for people who are unable to make their own antibodies. It is the mainstay of treatment for patients affected by primary antibody deficiency. In addition to immunoglobulin treatment, children may need to take antibiotics or antifungal medicines to prevent infections or treat them promptly when they occur. Regular monitoring and check-ups will help to catch infections early. If an autoimmune response occurs, this can be treated with steroid and/or biologic medicines to damp down the immune system so relieving the symptoms.

In some severely affected patients, NEMO deficiency syndrome is treated using a bone marrow or blood stem cell transplant. The aim is to replace the faulty immune system with an immune system from a healthy donor.

It is one of the 29 conditions currently recommended for newborn screening by the American College of Medical Genetics.

Low neutrophil counts are termed "neutropenia". This can be congenital (developed at or before birth) or it can develop later, as in the case of aplastic anemia or some kinds of leukemia. It can also be a side-effect of medication, most prominently chemotherapy. Neutropenia makes an individual highly susceptible to infections. It can also be the result of colonization by intracellular neutrophilic parasites.

In alpha 1-antitrypsin deficiency, the important neutrophil enzyme elastase is not adequately inhibited by alpha 1-antitrypsin, leading to excessive tissue damage in the presence of inflammation – the most prominent one being pulmonary emphysema.

In Familial Mediterranean fever (FMF), a mutation in the "pyrin" (or "marenostrin") gene, which is expressed mainly in neutrophil granulocytes, leads to a constitutively active acute-phase response and causes attacks of fever, arthralgia, peritonitis, and – eventually – amyloidosis.

Decreases in neutrophil function have been linked to hyperglycemia. Dysfunction in the neutrophil biochemical pathway myeloperoxidase as well as reduced degranulation are associated with hyperglycemia.

The Absolute neutrophil count (ANC) is also used in diagnosis and prognosis. ANC is the gold standard for determining severity of neutropenia, and thus neutropenic fever. Any ANC < 1500 cells / mm is considered neutropenia, but <500 cells / mm is considered severe. There is also new research tying ANC to myocardial infarction as an aid in early diagnosis.

The diagnosis of short-chain acyl-coenzyme A dehydrogenase deficiency is based on the following:

- Newborn screening test

- Genetic testing

- Urine test

There is a deficiency of malate in patients because fumarase enzyme can't convert fumarate into it therefore treatment is with oral malic acid which will allow the krebs cycle to continue, and eventually make ATP.