Combined immune deficiencies (CIDs) are a diverse group of inherited immune disorders characterized by impaired

T lymphocyte T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...

development, function, or both, with variable

B cell B cells, also known as B lymphocytes, are a type of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or inserted into the plasm ...

defects. The primary clinical manifestation of CID is

infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...

susceptibility. Clinical manifestations of combined immunodeficiencies vary greatly, ranging from

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

and

sinus infections Sinusitis, also known as rhinosinusitis, is an inflammation of the mucous membranes that line the sinuses resulting in symptoms that may include production of thick nasal mucus, nasal congestion, facial congestion, facial pain, facial pressure, lo ...

to opportunistic infections caused by

mycobacteria ''Mycobacterium'' is a genus of over 190 species in the phylum Actinomycetota, assigned its own family, Mycobacteriaceae. This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis ('' M. tuberculosis'') a ...

fungi A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and mold (fungus), molds, as well as the more familiar mushrooms. These organisms are classified as one ...

, and

vaccination Vaccination is the administration of a vaccine to help the immune system develop immunity from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...

reactions resulting in localized to systemic symptoms.

Antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

s and immunoglobulin replacement therapy are typically administered to patients as needed. Without

hematopoietic cell A blood cell (also called a hematopoietic cell, hemocyte, or hematocyte) is a cell produced through hematopoiesis and found mainly in the blood. Major types of blood cells include red blood cells (erythrocytes), white blood cells (leukocytes) ...

or other transplantation aimed at correcting the underlying pathophysiological defect, prognosis is frequently poor due to

T cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...

dysfunction.

Signs and symptoms

Patients with combined immune deficiencies typically exhibit recurrent

gastrointestinal The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. ...

and respiratory tract infections, which can be attributed to a wide variety of

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

. However, because of

dysfunction, patients frequently struggle to control

viral infections A viral disease (or viral infection) occurs when an organism's body is invaded by pathogenic viruses, and infectious virus particles (virions) attach to and enter susceptible cells. Examples include the common cold, gastroenteritis, COVID-19, ...

, particularly Epstein-Barr virus, which is extremely sensitive to cytolytic T cell dysfunction. Deficits in viral infection control may contribute to an increased likelihood of

malignancies Malignancy () is the tendency of a medical condition to become progressively worse; the term is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not ...

, particularly EBV1

lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph node ...

. Other intracellular

microbes A microorganism, or microbe, is an organism of microscopic size, which may exist in its single-celled form or as a colony of cells. The possible existence of unseen microbial life was suspected from antiquity, with an early attestation in ...

, such as

, can be difficult to control in CID patients, as can

opportunistic 300px, ''Opportunity Seized, Opportunity Missed'', engraving by Theodoor Galle, 1605 Opportunism is the practice of taking advantage of circumstances — with little regard for principles or with what the consequences are for others. Opport ...

or normally non-pathogenic infections caused by

Pneumocystis jirovecii ''Pneumocystis jirovecii'' (previously ''P. carinii'') is a yeast-like fungus of the genus ''Pneumocystis''. The causative organism of ''Pneumocystis'' pneumonia, it is an important human pathogen, particularly among immunocompromised hosts. P ...

Candida Candida, or Cándida (Spanish), may refer to: Biology and medicine * ''Candida'' (fungus), a genus of yeasts ** Candidiasis, an infection by ''Candida'' organisms * Malvasia Candida, a variety of grape Places * Candida, Campania, a ''comu ...

Diagnosis

When a clinical diagnosis of combined immunodeficiency is suspected, preliminary laboratory tests should be ordered. The patient's

complete blood count A complete blood count (CBC), also known as a full blood count (FBC) or full haemogram (FHG), is a set of medical laboratory tests that provide cytometry, information about the cells in a person's blood. The CBC indicates the counts of white blo ...

(CBC) reveals immunological changes. The absolute neutrophil and lymphocyte count should be determined based on the patient's age. In all patients,

HIV The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the im ...

should be ruled out. Specific immunological parameters should be evaluated by measuring

immunoglobulins An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that cause di ...

, vaccinal response after 6 months of life, and

flow cytometry Flow cytometry (FC) is a technique used to detect and measure the physical and chemical characteristics of a population of cells or particles. In this process, a sample containing cells or particles is suspended in a fluid and injected into the ...

measurement of larger leukocyte subtypes.

Treatment

Treatment for combined immunodeficiencies with defects in antibody production primarily consists of immunoglobulin replacement therapy. Susceptibility to

infections An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...

is an important feature of combined immunodeficiencies and influences patients' clinical evolution; as a result,

antimicrobial prophylaxis Antibiotic prophylaxis refers to, for humans, the prevention of infection complications using antimicrobial therapy (most commonly antibiotics). Antibiotic prophylaxis in domestic animal feed mixes has been employed in America since at least 1970 ...

is frequently used to prevent infections and their complications. For patients with severe and lethal forms of inborn errors of immunity, hematopoietic stem-cell transplantation is currently the curative treatment of choice.

Epidemiology

Globally, the reported incidence of CIDs ranges from 1:100,000 to 1:5000 live births; however, due to patient mortality prior to diagnosis, misdiagnoses of patients exhibiting unusual clinical manifestations, and incomplete national registries recording CID incidence, this is thought to be an underestimate of the true incidence. There has been reported to be a diagnostic delay of a few days to several years between the age at which the disease first manifests and the diagnosis of CID.

References

External links

{{Immune disorders Combined T and B–cell immunodeficiencies