T-cell immunodeficiency: types, signs of infection risk and how it is diagnosed and treated

The immune system has several arms. The MSD Manual divides primary immunodeficiency disorders by which part is affected: humoral immunity, involving B cells that make antibodies; cellular immunity, involving T cells that help identify and destroy foreign or abnormal cells; combined problems of both; phagocytes; and complement proteins. T-cell immunodeficiency is a disorder of the cellular arm. The affected component may be missing, reduced in number or abnormal and malfunctioning.

T-cell problems can be present from birth (primary) or develop later because of another illness or treatment (secondary). The MSD Manual notes problems with B cells are the most common primary immunodeficiencies, accounting for more than half, so pure T-cell disorders are comparatively uncommon.

GOSH describes severe combined immunodeficiency (SCID), in which lymphocytes (T-cells, B-cells and natural killer cells) are missing or not working properly, as a group of disorders with life-threatening infection risk.

GOSH explains that SCID is inherited, caused by a mutation in a child's genetic make-up that causes the absence or malfunction of a protein needed for the immune system to develop or work. Many different genes can be affected, giving different types, such as common gamma chain deficiency, adenosine deaminase (ADA) deficiency, JAK3 kinase deficiency, MHC class II deficiency and recombinase activating gene (RAG) deficiency. Knowing the exact cause matters because in some types there are specific treatments and because it allows accurate genetic counselling for future pregnancies.

The MSD Manual lists DiGeorge syndrome among T-cell disorders and says that doctors may recognise it from characteristic features such as low-set ears, a small receding jaw and wide-set eyes.

Secondary T-cell problems are more common overall. The MSD Manual says secondary immunodeficiency can result from prolonged or serious disorders such as diabetes or cancer, from medications and rarely from radiation therapy. It names HIV infection, cancers that affect the bone marrow such as leukaemia or lymphoma, undernutrition, and some infections such as measles and cytomegalovirus, and says secondary disorders also occur in older adults and people who are hospitalised.

The MSD Manual says people with an immunodeficiency tend to have one infection after another, usually respiratory first, and many eventually develop severe bacterial infections that persist, recur or lead to complications. Thrush may be an early sign. Infants or young children may have chronic diarrhoea and fail to thrive. It also cautions that having many colds does not necessarily suggest an immunodeficiency, because repeated exposure at day care or school is a more likely cause of frequent infections in children.

For SCID, GOSH says babies may seem well at birth and for the first few weeks because they are partly protected by antibodies from the mother. The first signs usually occur within the first three to six months: more frequent and more severe infections, severe and persistent thrush in the mouth or nappy area, poor feeding, chronic diarrhoea and poor weight gain, and skin rashes. GOSH says germs that do not cause disease in healthy people, such as Pneumocystis jirovecii, Aspergillus and cytomegalovirus, can cause severe infection, most frequently pneumonia, and that chickenpox and cold sore virus can be dangerous.

Seek urgent medical help (999 or A&E) for a baby or child who is struggling to breathe, is very drowsy or floppy, has a rash that does not fade or is rapidly worsening, or has a serious infection that is making them deteriorate quickly. GOSH says the first indication of SCID can be a serious infection that causes rapid deterioration requiring urgent admission and sometimes intensive care.

For persistent, severe or unusual infections without an emergency, see your GP. The MSD Manual says doctors suspect immunodeficiency when there are many recurrent infections, when infections are severe or unusual or caused by organisms that normally do not cause severe infection, when recurrent infections do not respond to treatment, or when family members also have frequent severe infections.

The MSD Manual says diagnosis involves blood tests, sometimes skin tests, a biopsy and sometimes genetic testing, once the doctor first suspects immunodeficiency. GOSH says SCID may be suspected from routine investigations, usually because of a low lymphocyte count in the blood, after which the infant is referred to a specialist immunology centre for confirmatory tests and to determine the type.

GOSH also describes a screening evaluation: it says an evaluation of screening for SCID in England began on 6 September 2021 as part of NHS newborn blood spot screening, initially for two years, and that midwives would say whether it was available locally. That information dates from 2021; check the current newborn screening position with your midwife or the NHS.

For SCID, GOSH says there are two specialist UK centres, Great Ormond Street Hospital in London and the Great North Children's Hospital in Newcastle. Immediate priorities are to protect the child from infection, with a room with filtered air, and to give antibiotics, antiviral and antifungal medicines, immunoglobulin replacement and, if needed, specially prepared blood transfusions. Definitive treatment is haematopoietic stem cell transplantation (HSCT), the most usual treatment, and gene therapy, which GOSH says is only suitable in a small number of specific conditions and is still being tested in clinical trials.

For acquired T-cell problems, treatment targets the cause, for example antiviral therapy for HIV, treatment of the underlying cancer, adjusting immune-suppressing medicines or improving nutrition. In all cases your specialist will advise on protective measures, vaccination and what to do when an infection starts.

GOSH says that before modern treatment most babies with SCID did not survive beyond their first year, but that today treatment can in many cases cure the disorder. Outcomes for other T-cell disorders depend on the specific condition. Early diagnosis, before serious infections have caused damage, makes treatment more likely to succeed.

In the NHS, diagnosis and management are by clinical immunology and paediatric immunology services, with infectious diseases and HIV services for acquired causes. Private consultations can provide assessment and testing, but the treatment of severe disorders such as SCID is provided in the specialist NHS centres.