The mainstay of treatment consists of thymectomy and immunoglobulin replacement with IVIG (Kelesidis, 2010). Immunodeficiency does not resolve after thymectomy (Arnold, 2015). To treat the autoimmune component of the disease, immune-suppression is sometimes used and it is often challenging to determine if a patient’s symptoms are infectious or autoimmune (Arnold, 2015).

Patients should have serological testing for antibodies to toxoplasma and cytomegalovirus. If receiving a transfusion, CMV negative blood should be used in those with negative serological testing. Live vaccines should also be avoided (Kelesidis, 2010). The CDC recommends pneumococcal, meningococcal, and Hib vaccination in those with diminished humoral and cell-mediated immunity (Hamborsky, 2015).

Some have advocated treating prophylactically with TMP-SMX if CD4 counts are lower than 200 cells/mm^3, similar to AIDS patients (Kelesidis, 2010).

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.

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.

Bone marrow transplant may be possible for Severe Combined Immune Deficiency and other severe immunodeficiences.

Virus-specific T-Lymphocytes (VST) therapy is used for patients who have received hematopoietic stem cell transplantation that has proven to be unsuccessful. It is a treatment that has been effective in preventing and treating viral infections after HSCT. VST therapy uses active donor T-cells that are isolated from alloreactive T-cells which have proven immunity against one or more viruses. Such donor T-cells often cause acute graft-versus-host disease (GVHD), a subject of ongoing investigation. VSTs have been produced primarily by ex-vivo cultures and by the expansion of T-lymphocytes after stimulation with viral antigens. This is carried out by using donor-derived antigen-presenting cells. These new methods have reduced culture time to 10–12 days by using specific cytokines from adult donors or virus-naive cord blood. This treatment is far quicker and with a substantially higher success rate than the 3–6 months it takes to carry out HSCT on a patient diagnosed with a primary immunodeficiency. T-lymphocyte therapies are still in the experimental stage; few are even in clinical trials, none have been FDA approved, and availability in clinical practice may be years or even a decade or more away.

Treatment for "B cell deficiency"(humoral immune deficiency) depends on the cause, however generally the following applies:

- Treatment of infection(antibiotics)

- Surveillance for malignancies

- Immunoglobulin replacement therapy

Treatment consists of immunoglobulin replacement therapy, which replenishes Ig subtypes that the person lack. This treatment is given at frequent intervals for life, and is thought to help reduce bacterial infections and boost immune function. Before therapy begins, plasma donations are tested for known blood-borne pathogens, then pooled and processed to obtain concentrated IgG samples. Infusions can be administered in three different forms: intravenously (IVIg):, subcutaneously (SCIg), and intramuscularly (IMIg).

The administration of intravenous immunoglobulins requires the insertion of a cannula or needle in a vein, usually in the arms or hands. Because highly concentrated product is used, IVIg infusions take place every 3 to 4 weeks. Subcutaneous infusions slowly release the Ig serum underneath the skin, again through a needle, and takes place every week. Intramuscular infusions are no longer widely used, as they can be painful and are more likely to cause reactions.

People often experience adverse side effects to immunoglobulin infusions, including:

- swelling at the insertion site (common in SCIG)

- chills

- headache

- nausea (common in IVIG)

- fatigue (common in IVIG)

- muscle aches and pain, or joint pain

- fever (common in IVIG and rare in SCIG)

- hives (rare)

- thrombotic events (rare)

- aseptic meningitis (rare, more common in people with SLE)

- anaphylactic shock (very rare)

In addition to Ig replacement therapy, treatment may also involve immune suppressants, to control autoimmune symptoms of the disease, and high dose steroids like corticosteroids. In some cases, antibiotics are used to fight chronic lung disease resulting from CVID. The outlook for people varies greatly depending on their level of lung and other organ damage prior to diagnosis and treatment.

In terms of treatment the following are done to manage the IPEX syndrome in those affected individuals(corticosteroids are the first treatment that is used):

- TPN(nutritional purpose)

- Cyclosporin A and FK506

- Sirolimus(should FK506 prove non-effective)

- Granulocyte colony stimulating factor

- Bone marrow transplant

- Rituximab

Prognosis depends greatly on the nature and severity of the condition. Some deficiencies cause early mortality (before age one), others with or even without treatment are lifelong conditions that cause little mortality or morbidity. Newer stem cell transplant technologies may lead to gene based treatments of

debilitating and fatal genetic immune deficiencies. Prognosis of acquired immune deficiencies depends on avoiding or treating the causative agent or

condition (like AIDS).

Nonsteroidal anti-inflammatory drugs (NSAIDs) may be used to treat musculoskeletal symptoms. For individuals with severe complications, corticosteroids or immunosuppressive drugs may be prescribed, and sometimes IVIG (intravenous immunoglobulin). Also, disease-modifying antirheumatic drugs (DMARDs) such as methotrexate may be helpful. Hydroxychloroquine (Plaquenil) is another option and is generally considered safer than methotrexate. However, these prescribed drugs have a range of side effects such as nausea, loss of appetite, dizziness, hair loss, stomach aches/cramps, headache, liver toxicity, and increased risk of infections. Also, people who take drugs to suppress the immune system are more likely to develop cancer later.

The most common treatment for SCID is bone marrow transplantation, which has been successful using either a matched related or unrelated donor, or a half-matched donor, who would be either parent. The half-matched type of transplant is called haploidentical. Haploidentical bone marrow transplants require the donor marrow to be depleted of all mature T cells to avoid the occurrence of graft-versus-host disease (GVHD). Consequently, a functional immune system takes longer to develop in a patient who receives a haploidentical bone marrow transplant compared to a patient receiving a matched transplant. David Vetter, the original "bubble boy", had one of the first transplantations, but eventually died because of an unscreened virus, Epstein-Barr (tests were not available at the time), in his newly transplanted bone marrow from his sister, an unmatched bone marrow donor. Today, transplants done in the first three months of life have a high success rate. Physicians have also had some success with "in utero" transplants done before the child is born and also by using cord blood which is rich in stem cells. "In utero" transplants allow for the fetus to develop a functional immune system in the sterile environment of the uterus; however complications such as GVHD would be difficult to detect or treat if they were to occur.

More recently gene therapy has been attempted as an alternative to the bone marrow transplant. Transduction of the missing gene to hematopoietic stem cells using viral vectors is being tested in ADA SCID and X-linked SCID. In 1990, four-year-old Ashanthi DeSilva became the first patient to undergo successful gene therapy. Researchers collected samples of DeSilva's blood, isolated some of her white blood cells, and used a retrovirus to insert a healthy adenosine deaminase (ADA) gene into them. These cells were then injected back into her body, and began to express a normal enzyme. This, augmented by weekly injections of ADA, corrected her deficiency. However, the concurrent treatment of ADA injections may impair the success of gene therapy, since transduced cells will have no selective advantage to proliferate if untransduced cells can survive in the presence of the injected ADA.

In 2000, a gene therapy "success" resulted in SCID patients with a functional immune system. These trials were stopped when it was discovered that two of ten patients in one trial had developed leukemia resulting from the insertion of the gene-carrying retrovirus near an oncogene. In 2007, four of the ten patients have developed leukemias. Work aimed at improving gene therapy is now focusing on modifying the viral vector to reduce the likelihood of oncogenesis and using zinc-finger nucleases to more specifically target gene insertion. No leukemia cases have yet been seen in trials of ADA-SCID, which does not involve the "gamma c" gene that may be oncogenic when expressed by a retrovirus.

Trial treatments of SCID have been gene therapy's first success; since 1999, gene therapy has restored the immune systems of at least 17 children with two forms (ADA-SCID and X-SCID) of the disorder.

There are also some non-curative methods for treating SCID. Reverse isolation involves the use of laminar air flow and mechanical barriers (to avoid physical contact with others) to isolate the patient from any harmful pathogens present in the external environment. A non-curative treatment for patients with ADA-SCID is enzyme replacement therapy, in which the patient is injected with polyethyleneglycol-coupled adenosine deaminase (PEG-ADA) which metabolizes the toxic substrates of the ADA enzyme and prevents their accumulation. Treatment with PEG-ADA may be used to restore T cell function in the short term, enough to clear any existing infections before proceeding with curative treatment such as a bone marrow transplant.

Treatments for autoimmune disease have traditionally been immunosuppressive, anti-inflammatory, or palliative. Managing inflammation is critical in autoimmune diseases. Non-immunological therapies, such as hormone replacement in Hashimoto's thyroiditis or Type 1 diabetes mellitus treat outcomes of the autoaggressive response, thus these are palliative treatments. Dietary manipulation limits the severity of celiac disease. Steroidal or NSAID treatment limits inflammatory symptoms of many diseases. IVIG is used for CIDP and GBS. Specific immunomodulatory therapies, such as the TNFα antagonists (e.g. etanercept), the B cell depleting agent rituximab, the anti-IL-6 receptor tocilizumab and the costimulation blocker abatacept have been shown to be useful in treating RA. Some of these immunotherapies may be associated with increased risk of adverse effects, such as susceptibility to infection.

Helminthic therapy is an experimental approach that involves inoculation of the patient with specific parasitic intestinal nematodes (helminths). There are currently two closely related treatments available, inoculation with either Necator americanus, commonly known as hookworms, or Trichuris Suis Ova, commonly known as Pig Whipworm Eggs.

T cell vaccination is also being explored as a possible future therapy for autoimmune disorders.

Vitamin D/Sunlight

Omega-3 Fatty Acids

Probiotics/Microflora

Antioxidants

In women with SS, vaginal dryness, vulvodynia and dyspareunia (painful sexual intercourse) are often reported; personal lubricants are recommended to help lessen irritation or pain that may result from dryness in the vaginal and vulva areas.

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

In terms of the treatment for ativated PI3K delta syndrome, generally primary immunodeficiencies see the following used:

- Bacterial infection should be treated rapidly(with antibiotics)

- Antiviral therapy

- Modify lifestyle(exposure to pathogens need to be minimized)

Autoimmune polyendocrine syndrome type 1 treatment is based on the symptoms that are presented by the affected individual, additionally there is:

- Hormone replacement

- Systemic antifungal treatment

- Immunosuppressive treatment

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

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.

In terms of the management of T cell deficiency for those individuals with this condition the following can be applied:

- Killed vaccines should be used(not "live vaccines" in T cell deficiency)

- Bone marrow transplant

- Immunoglobulin replacement

- Antiviral therapy

- Supplemental nutrition

In terms of treatment for individuals with Nezelof syndrome, which was first characterized in 1964, includes the following(how effective bone marrow transplant is uncertain) :

- Antimicrobial therapy

- IV immunoglobulin

- Bone marrow transplantation

- Thymus transplantation

- Thymus factors

Infusions of immune globulin can reduce the frequency of bacterial infections, and G-CSF or GM-CSF therapy improves blood neutrophil counts.

As WHIM syndrome is a molecular disease arising from gain-of-function mutations in CXCR4, preclinical studies identified plerixafor, a specific CXCR4 antagonist, as a potential mechanism-based therapeutic for the disease. Two subsequent clinical trials involving a handful of patients with WHIM syndrome demonstrated that plerixafor could increase white blood cell counts and continues to be a promising targeted therapy.

A woman with spontaneous remission of her WHIM syndrome due to Chromothripsis in one of her blood stem cells has been identified.

In support of these studies, a 2014 phase I clinical trial treated 3 patients diagnosed with WHIM syndrome with plerixafor twice a day for 6 months. All three patients presented with multiple reoccurring infections before treatment and all had an increase in their white blood cell count post treatment. One patient (P3) had a decrease in his infections by 40% while the remaining 2 patients (P1 and P2) had no infections throughout the entirety of the treatment. Plerixafor may also proof to have anti-human papillomavirus (HPV) properties as all patients experienced a shrinkage or complete disappearance of their warts. While this treatment shows promise in treating neutropenia (decreased white blood cells), this trial showed no increase of immune globulins in the body. A phase III clinical trial has been approved to compare the infection prevention ability of plerixafor versus the current treatment of G-CSF in patients with WHIM.

Treatment is by parenteral administration of gamma globulins, either monthly intravenously, or, more recently, by weekly self-administered hypodermoclysis. In either case, mild allergic reactions (generalized pruritus, urticaria) are common, and are usually manageable with oral diphenhydramine.

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.

Current research is aimed at studying large cohorts of people with CVID in an attempt to better understand age of onset, as well as mechanism, genetic factors, and progression of the disease.

Funding for research in the US is provided by the National Institutes of Health. Key research in the UK was previously funded by the Primary Immunodeficiency Association (PiA) until its closure in January 2012, and funding is raised through the annual Jeans for Genes campaign. Current efforts are aimed at studying the following:

- Causes of complications. Little is known about why such diverse complications arise during treatment

- Underlying genetic factors. Though many polymorphisms and mutations have been identified, their respective roles in CVID development are poorly understood, and not represented in all people with CVID.

- Finding new ways to study CVID. Given that CVID arises from more than one gene, gene knock-out methods are unlikely to be helpful. It is necessary to seek out disease related polymorphisms by screening large populations of people with CVID, but this is challenging given the rarity of the disease.

There are many lymphoproliferative disorders that are associated with organ transplantation and immunosuppressant therapies. In most reported cases, these cause B cell lymphoproliferative disorders; however, some T cell variations have been described. The T cell variations are usually caused by the prolonged use of T cell suppressant drugs, such as sirolimus, tacrolimus, or ciclosporin.