Prognosis is excellent, although there is an association with autoimmune disease. Of note, selective IgA deficiency can complicate the diagnosis of one such condition, celiac disease, as the deficiency masks the high levels of certain IgA antibodies usually seen in celiac disease.

As opposed to the related condition CVID, selective IgA deficiency is not associated with an increased risk of cancer.

Patients with Selective IgA deficiency are at risk of anaphylaxis from blood transfusions. These patients should receive IgA free containing blood products and ideally blood from IgA-deficient donors.

Prevalence varies by population, but is on the order of 1 in 100 to 1 in 1000 people, making it relatively common for a genetic disease.

SigAD occurs in 1 of 39 to 57 patients with celiac disease. This is much higher than the prevalence of selective IgA deficiency in the general population. It is also significantly more common in those with type 1 diabetes.

It is more common in males than in females.

A survey of 10,000 American households revealed that the prevalence of diagnosed primary immunodeficiency approaches 1 in 1200. This figure does not take into account people with mild immune system defects who have not received a formal diagnosis.

Milder forms of primary immunodeficiency, such as selective immunoglobulin A deficiency, are fairly common, with random groups of people (such as otherwise healthy blood donors) having a rate of 1:600. Other disorders are distinctly more uncommon, with incidences between 1:100,000 and 1:2,000,000 being reported.

By definition, primary immune deficiencies are due to genetic causes. They may result from a single genetic defect, but most are multifactorial. They may be caused by recessive or dominant inheritance. Some are latent, and require a certain environmental trigger to become manifest, like the presence in the environment of a reactive allergen. Other problems become apparent due to aging of bodily and cellular maintenance processes.

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.

In the world less than 1 in 1.00.000 have HIDS [5]. 200 individuals throughout the world do suffer from MVK.

Serology (detection on antibodies to a specific pathogen or antigen) is often used to diagnose viral diseases. Because XLA patients lack antibodies, these tests always give a negative result regardless of their real condition. This applies to standard HIV tests. Special blood tests (such as the western blot based test) are required for proper viral diagnosis in XLA patients.

It is not recommended and dangerous for XLA patients to receive live attenuated vaccines such as live polio, or the measles, mumps, rubella (MMR vaccine). Special emphasis is given to avoiding the oral live attenuated SABIN-type polio vaccine that has been reported to cause polio to XLA patients. Furthermore, it is not known if active vaccines in general have any beneficial effect on XLA patients as they lack normal ability to maintain immune memory.

XLA patients are specifically susceptible to viruses of the Enterovirus family, and mostly to: polio virus, coxsackie virus (hand, foot, and mouth disease) and Echoviruses. These may cause severe central nervous system conditions as chronic encephalitis, meningitis and death. An experimental anti-viral agent, pleconaril, is active against picornaviruses. XLA patients, however, are apparently immune to the Epstein-Barr virus (EBV), as they lack mature B cells (and so HLA co-receptors) needed for the viral infection. Patients with XLA are also more likely to have a history of septic arthritis.

It is not known if XLA patients are able to generate an allergic reaction, as they lack functional IgE antibodies.There is no special hazard for XLA patients in dealing with pets or outdoor activities. Unlike in other primary immunodeficiencies XLA patients are at no greater risk for developing autoimmune illnesses.

Agammaglobulinemia (XLA) is similar to the primary immunodeficiency disorder Hypogammaglobulinemia (CVID), and their clinical conditions and treatment are almost identical. However, while XLA is a congenital disorder, with known genetic causes, CVID may occur in adulthood and its causes are not yet understood.

XLA was also historically mistaken as Severe Combined Immunodeficiency (SCID), a much more severe immune deficiency ("Bubble boys").A strain of laboratory mouse, XID, is used to study XLA. These mice have a mutated version of the mouse Btk gene, and exhibit a similar, yet milder, immune deficiency as in XLA.

Mevalonate kinase deficiency, also called mevalonic aciduria and hyper immunoglobin D syndrome is an autosomal recessive metabolic disorder that disrupts the biosynthesis of cholesterol and isoprenoids.

It is characterized by an elevated level of immunoglobin D in the blood.

The enzyme is involved in biosynthesis of cholesterols and isoprenoids. The enzyme is necessary for the conversion of mevalonate to mevalonate-5-phosphate in the presence of Mg2+ [Harper’s biochemistry manual]. Mevalonate kinase deficiency causes the accumulation of mevalonate in urine and hence the activity of the enzyme is again reduced Mevalonate kinase deficiency. It was first described as HIDS in 1984.

Hypergammaglobulinemia is a medical condition with elevated levels of gamma globulin.

It is a type of immunoproliferative disorder.

CVID has an estimated prevalence of about 1:50,000 in caucasians. The disease seems to be less prevalent amongst Asians and African-Americans. Males and females are equally affected; however, among children, boys predominate. A recent study of people in European with primary immunodeficiencies found that 30% had CVID, as opposed to a different immunodeficiency. 10-25% of people inherited the disease, typically through autosomal-dominant inheritance. Given the rarity of the disease, it is not yet possible to generalize on disease prevalence among ethnic and racial groups. CVID shortens the life-span; the median age of death for men and women is 42 and 44 years old, respectively. Those people with accompanying disorders had the worst prognosis and those people with CVID only had frequent infections had the longest survival rates, with life expectancy almost equalling that of the general UK population. Additionally, people with CVID with one or more noninfectious complications have an 11 times higher risk of death as compared to people with only infections.

Hypergammaglobulinemia is a condition that is characterized by the increased levels of a certain immunoglobulin in the blood serum. The name of the disorder refers to an excess of proteins after serum protein electrophoresis (found in the gammaglobulin region).

Most hypergammaglobulinemias are caused by an excess of immunoglobulin M (IgM), because this is the default immunoglobulin type prior to class switching. Some types of hypergammaglobulinemia are actually caused by a deficiency in the other major types of immunoglobulins, which are IgA, IgE and IgG.

There are 5 types of hypergammaglobulinemias associated with hyper IgM.

MeSH considers hyper IgM syndrome to be a form of dysgammaglobulinemia, not a form of hypergammaglobulinemia .

Children with DOCK8 deficiency do not tend to live long; sepsis is a common cause of death at a young age. CNS and vascular complications are other common causes of death.

In the U.S. this defect occurs in about 1 in 70,000, with the majority of cases presenting in early life.

Furthermore, SCID has an incidence of approximately 1 in 66,000 in California

IgG deficiency (Selective deficiency of immunoglobulin G) is a form of dysgammaglobulinemia where the proportional levels of the IgG isotype are reduced relative to other immunoglobulin isotypes. IgG deficiency is often found in children as transient hypogammaglobulinemia of infancy (THI), which may occur with or without additional decreases in IgA or IgM.

IgG has four subclasses: IgG, IgG, IgG, and IgG. It is possible to have either a global IgG deficiency, or a deficiency of one or more specific subclasses of IgG. The main clinically relevant form of IgG deficiency is IgG. IgG deficiency is not usually encountered without other concomitant immunoglobulin deficiencies, and IgG deficiency is very common but usually asymptomatic.

IgG1 is present in the bloodstream at a percentage of about 60-70%, IgG2-20-30%, IgG3 about 5-8 %, and IgG4 1-3 %. IgG subclass deficiencies affect only IgG subclasses (usually IgG2 or IgG3), with normal total IgG and IgM immunoglobulins and other components of the immune system being at normal levels. These deficiencies can affect only one subclass or involve an association of two subclasses, such as IgG2 and IgG4. IgG deficiencies are usually not diagnosed until the age of 10. Some of the IgG levels in the blood are undetectable and have a low percentage such as IgG4, which makes it hard to dertermine if a deficiency is actually present. IgG subclass deficiencies are sometimes correlated with bad responses to pneumoccal polyscaccharides, especially IgG2 and or IgG4 deficiency. Some of these deficiencies are also involved with pancreatitis and have been linked to IgG4 levels.

Isolated primary immunoglobulin M deficiency (or selective IgM immunodeficiency (SIgMD)) is a poorly defined dysgammaglobulinemia characterized by decreased levels of IgM while levels of other immunoglobulins are normal. The immunodeficiency has been associated with some clinical disorders including recurrent infections, atopy, Bloom's syndrome, celiac disease, systemic lupus erythematosus and malignancy, but, surprisingly, SIgMD seems to also occur in asymptomatic individuals. High incidences of recurrent upper respiratory tract infections (77%), asthma (47%) and allergic rhinitis (36%) have also been reported. SIgMD seems to be a particularly rare antibody deficiency with a reported prevalence between 0.03% (general population) and 0.1% (hospitalized patients).

The cause of selective IgM deficiency remains unclear, although various mechanisms have been proposed, such as an increase in regulatory T cell functions, defective T helper cell functions and impaired terminal differentiation of B lymphocytes into IgM-secreting cells among others. It is however puzzling that class switching seems to happen normally (serum levels of other antibodies are normal), while dysfunctioning of IgM synthesis is expected to occur together with abnormalities in other immunoglobulins. Notwithstanding a clear pathogenesis and commonly accepted definition, a cutoff for SIgMD could be the lower limit of the serum IgM reference range, such as 43 mg/dL in adults or even 20 mg/dL.

DOCK8 deficiency is very rare, estimated to be found in less than one person per million; there have been 32 patients diagnosed as of 2012.

Different genetic defects cause HIgM syndrome, the vast majority are inherited as an X-linked recessive genetic trait and most sufferers are male.

IgM is the form of antibody that all B cells produce initially, before they undergo class switching due to exposure to a recognized antigen. Healthy B cells efficiently switch to other types of antibodies as needed to attack invading bacteria, viruses, and other pathogens. In people with hyper IgM syndromes, the B cells keep making IgM antibodies because they can't switch to a different antibody. This results in an overproduction of IgM antibodies and an underproduction of IgA, IgG, and IgE.

GSE can result in high risk pregnancies and infertility. Some infertile women have GSE and iron deficiency anemia others have zinc deficiency and birth defects may be attributed to folic acid deficiencies.

It has also been found to be a rare cause of amenorrhea.

A 2006 study of 279 patients found that of those with symptoms (185, 66%), 95% had suffered an encephalopathic crises usually with following brain damage. Of the persons in the study, 49 children died and the median age of death was 6.6 years. A Kaplan-Meier analysis of the data estimated that about 50% of symptomatic cases would die by the age of 25.

Hyper IgM syndromes is a group of primary immune deficiency disorders characterized by defective CD40 signaling; "via" B cells affecting class switch recombination (CSR) and somatic hypermutation. Immunoglobulin (Ig) class switch recombination deficiencies are characterized by elevated serum Immunoglobulin M (IgM) levels and a considerable deficiency in Immunoglobulins G (IgG), A (IgA) and E (IgE). As a consequence, people with HIGM have decreased concentrations of serum IgG and IgA and normal or elevated IgM, leading to increased susceptibility to infections.

XLA diagnosis usually begins due to a history of recurrent infections, mostly in the respiratory tract, through childhood. This is due to humoral immunodeficiency. The diagnosis is probable when blood tests show the complete lack of circulating B cells (determined by the B cell marker CD19 and/or CD20), as well as low levels of all antibody classes, including IgG, IgA, IgM, IgE and IgD.

When XLA is suspected, it is possible to do a Western Blot test to determine whether the Btk protein is being expressed. Results of a genetic blood test confirm the diagnosis and will identify the specific Btk mutation, however its cost prohibits its use in routine screening for all pregnancies. Women with an XLA patient in their family should seek genetic counseling before pregnancy.Although the symptoms of a XLA and other primary immune diseases (PID) include repeated and often severe infections, the average time for a diagnosis of a PID can be up to 10 years.

Cause of this deficiency is divided into "primary" and "secondary":

- Primary the International Union of Immunological Societies classifies primary immune deficiencies of the humoral system as follows:

- Secondary secondary (or acquired) forms of humoral immune deficiency are mainly due to hematopoietic malignancies and infections that disrupt the immune system:

LRBA deficiency is a rare genetic disorder of the immune system. This disorder is caused by a mutation in the gene "LRBA". LRBA stands for “Lipopolysaccharide (LPS)-responsive vesicle trafficking, beach- and anchor-containing” gene. This condition is characterized by autoimmunity, lymphoproliferation, and immune deficiency. It was first described by Gabriela Lopez-Herrera from University College London in 2012. Investigators in the laboratory of Dr. Michael Lenardo at National Institute of Allergy and Infectious Diseases, the National Institutes of Health and Dr. Michael Jordan at Cincinnati Children’s Hospital Medical Center later described this condition and therapy in 2015.

Avitaminosis. Avitaminosis caused by malabsorption in GSE can result in decline of fat soluble vitamins and vitamin B, as well as malabsorption of essential fatty acids. This can cause a wide variety of secondary problems. Hypocalcinemia is also associated with GSE. In treated GSE, the restrictions on diet as well as reduced absorption as a result of prolonged damage may result in post treatment deficiencies.

- Vitamin A – Poor absorption of vitamin A has been seen in coeliac disease. and it has been suggested that GSE-associated cancers of the esophagus may be related to vitamin A deficiency

- Folate deficiency – Folate deficiency is believed to be primary to the following secondary conditions:

- Megaloblastic anemia

- Calcification of brain channels – epilepsy, dementia, visual manifestations.

- B deficiency. Vitamin B deficiency can result in neuropathies and increases in pain sensitivity. may explain some of the peripheral neuropathies, pain and depression associated with GSE.

- B deficiency

- Megaloblastic anemia

- Pernicious anemia

- Vitamin D deficiency. Vitamin D deficiency can result in osteopenia and osteoporosis

- Hypocalcemia

- Vitamin K – Coeliac disease has been identified in patients with a pattern of bleeding that treatment of vitamin K increased levels of prothrombin.

- Vitamin E – deficiency of vitamin E can lead to CNS problems and possibly associated with myopathy

Mineral deficiencies. GSE is associated with the following mineral deficiencies:

- Calcium – Hypocalcemia causing Oesteopenia

- Magnesium – hypomagnesemia, may lead to parathyroid abnormalities.

- Iron – Iron deficiency anemia

- Phosphorus – hypophosphatemia, causing Oesteopenia

- Zinc – Zinc deficiencies are believed to be associated with increased risk of Esophagus Carcinoma

- Copper – deficiency

- Selenium – deficiency – Selenium and Zinc deficiencies may play a role increasing risk of cancer. Selenium deficiency may also be an aggravating factor for autoimmune hyperthyroidism (Graves disease).

Blood factors

- Carnitine – deficiency.

- Prolactin – deficiency (childhood).

- homocysteine – excess.

In terms of diagnosis of "humoral immune deficiency" depends upon the following:

- Measure "serum immunoglobulin levels"

- B cell count

- Family medical history