Immunodeficiency Syndromes, HIV and AIDS: Immunodeficiency Syndromes

Chapter 15
Immunodeficiency Syndromes, HIV and AIDS

Natalie Yerlett, Julie Lanigan and Lisa Cooke

Immunodeficiency Syndromes

Natalie Yerlett


In an environment abundant with microorganisms, the immune system acts to protect the body from their potential harm. The human immune system has two functionalities, different, but both complementing each other to enhance effectiveness.

‘Innate’ immunity is the body’s first line defence, immediately having phagocytic cells ready to engulf and digest microorganisms. This response does not rely upon previous exposure to the antigen and does not produce antigen specific antibodies. Due to this, innate immunity is crucial to survival in early life. Innate immune responses are important in containing an infection and include complement cascade reactions and phagocytic cytokine release to induce inflammation. Innate immunity is non-specific and does not confer lifelong immunity to a repeat infection. These first line responses are triggered whilst awaiting the second line adaptive immune response [1].

‘Adaptive’ immunity is the more specific, tailored second line defence system. This enables the body to recognise and remember specific pathogens and subsequently mount a stronger immune response on each further exposure. Central to this is the production of an array of immune cells: B cells, T cells and natural killer (NK) cells, some of which produce specific antibodies to a particular antigen [1]. Adaptive immunity is paramount after infancy.

There are four main types of pathogens that should illicit an immune response:

  • fungi, e.g. Aspergillus fumigatus
  • parasites, e.g. Leishmania donovani
  • bacteria (extracellular or intracellular), e.g. Streptococcus pneumonia
  • viruses, e.g. influenza, cytomegalovirus

Defects or failures in any part of the complex immune system may lead to immune-pathological reactions and disease, often as a result of not being able to mount an immune response against an antigen, thus allowing it to successfully infiltrate and cause harm. Disorders of the immune system can be:

  • primary genetic mutations where elements of the immune cell nomenclature can be missing altogether
  • secondary to immune suppression therapy

These can be differentiated into disorders of B cell maturation and/or their ability to produce antibodies; T cell defects; combined T cell/B cell defects; disorders of phagocytes; complement deficiencies [1, 2].

Common immunodeficiency syndromes are listed in Table 15.1 together with their possible dietetic considerations.

Table 15.1 Summary of some immunodeficiency syndromes and possible dietetic considerations

Immunodeficiency Possible dietetic considerations
B cell defects
IgA deficiency Malabsorption, coeliac disease [4], gastrointestinal infection
IgG subclass deficiency Malabsorption, possible food allergy/colitis [9, 10]
Common variable immunodeficiency Abdominal pain, diarrhoea [28]
T cell defects
Autoimmune enteropathy Protracted diarrhoea of infancy, severe faltering growth, often failure of normal nutritional interventions [12, 13], hypoallergenic diet may be required
Class II MHC deficiency Chronic diarrhoea, severe infections
Wiskott–Aldrich syndrome Malabsorption, bloody diarrhoea [1]
T and B lymphocyte defects
SCID Diarrhoea, malabsorption, vomiting, GORD, infectious diarrhoea, faltering growth, increased nutritional requirements [20], hydrolysed protein formulas often required
Autosomal recessive Increased nutritional requirements
X-linked ADA, PNP deficiency, Omenn syndrome Skin losses, possible fluid/electrolyte imbalance
Phagocyte defects
Chronic granulomatous disease Diarrhoea, protein-losing enteropathy, pancolitis, frequent infections, intolerance of high feed volume, increased nutritional requirements requiring early use of nutrient dense enteral feeds [1, 19]
Leucocyte adhesion deficiency Mucosal infection and inflammation [19]

MHC major histocompatability complex; SCID, severe combined immune deficiency; GORD, gastro-oesophageal reflux disease; ADA, adenosine deaminase; PNP, purine nucleoside phosphorylase.

B and T cells

B cells

B cells are derived from haematopoietic stem cells in the bone marrow and remain there during maturation. B cells make up a ‘humoral’ immune response and their main function is to produce antibodies (immunoglobulins), namely IgA, IgD, IgG, IgM and IgE [1]. Therefore, B cells help to protect against extracellular pathogens, e.g. bacteria. There are two types of B cells:

  • B1 cells—are polyspecific with low affinity for many antigens
  • B2 cells—are constantly renewed in the bone marrow

B2 cells then progress through a further maturation process, which results in more specific B cell subsets [1]. These include:

  • plasma B cells (effector B cells)—already exposed to antigens, subsequently producing and secreting antibodies
  • memory B cells—made from activated B cells specific to a previous antigen; they are secreted quickly on encounter with the same antigen for the second time
  • marginal zone B cells—resident in the spleen
  • follicular B cells—resident in lymphoid tissues

B cell defects

B cell defects can range in type and severity. They may encompass:

  • absent B cells—severe reduction in all antibodies such as XLA [1, 2]
  • low B cell count but deficient B cell subclass, resulting in a variable degree deficiency such as low IgA/IgG
  • normal B cell count but with light chain deficiency/isotype—selective IgA deficiency

Selective IgA deficiency

IgA deficiency is the most common of the primary immune deficiency diseases. Patients may have a deficiency or a total absence of IgA, but usually have normal levels of the other immunoglobulins. Patients may be asymptomatic with ‘silent IgA deficiency’ or may require immunoglobulin treatment. IgA acts to protect mucosal surfaces; deficiency therefore leads to recurrent or chronic infections such as sinusitis, pneumonia, bronchitis and gastrointestinal infections.

The incidence of IgA deficiency in the general population is 1 in 700 people of European origin [3]. The prevalence of coeliac disease is up to 30% higher in patients with IgA deficiency compared with the general population [4], and this IgA deficiency persists when following a gluten free diet despite the return of a normal mucosa [5]. IgA antibodies against both tissue transglutaminase (tTG) and endomysial antibodies (EMA) are relied upon for serum screening of coeliac disease; therefore patients with IgA deficiency will not have a reliable tTG/EMA serum level and should have IgG tTG and EMA testing when available [6]. IgA plays a vital role in mucosal integrity; therefore it is also associated with the onset of food allergy [7].

IgG and IgG subclass deficiency

Children may have deficiencies in one or more of the IgG subclass (IgG1–4). Clinical presentation depends on the severity and combination of the deficiency, with some individuals being asymptomatic. Most commonly, children may present with recurrent infections [8]. It has been shown previously that patients with IgG deficiency may present with food allergy or food allergic colitis [9]; however, the literature in this area is limited. Food allergy testing involving IgG is not recommended [10]. The dietetic management of food allergy is described in Chapters 7 and 14.

T cells

T cells develop from haemopoietic stem cells in bone marrow which then migrate to the thymus. Here, they undergo maturation, differentiation into T cell types and finally undergo positive/negative selection to ensure that the resulting T cells will not over- or under-recognise host ‘self’ antigens. T cells illicit a ‘cell mediated’, intracellular immune response; therefore they can help to fight off intracellular pathogens such as viruses. There are three main categories of T cells [1]:

  • naïve T cells
  • memory T cells
  • effector T cells

T cell defects

T cell defects range in type and severity, for example:

  • complete insufficiency of T cell/T cell function, with/without concurrent B cell defect such as severe combined immune deficiency (SCID), including Omenn syndrome and major histocompatibility complex (MHC) Class II deficiency
  • partial or complete insufficiency of T cell function such as DiGeorge syndrome (often associated with absent thymus) or Wiskott–Aldridge syndrome
  • T cell dysregulation, i.e. autoimmune enteropathy

Autoimmune enteropathy

A primary immune dysregulation can result in immune mediated damage to the intestinal mucosa, commonly presenting with protracted diarrhoea of infancy and malabsorption [11]. The disease may be caused by immune dysfunction of varying natures, including activation of mucosal T cells causing persistent damage to the gut mucosa [12] or by auto-antibodies present on the gut mucosa [11]. Severe inflammation, villous atrophy with crypt hyperplasia and increased mitosis may be seen histologically. These changes in the small intestinal mucosa may resemble those found in coeliac disease [13]. Such infants present with severe faltering growth and may be unresponsive to normal enteral nutritional interventions [14]. Intense nutritional management is crucial as poor nutritional status can worsen mucosal integrity. In such cases immunosuppression is often required to control the disease. In patients with life threatening autoimmune enteropathy resulting from a primary autoimmune dysregulation, and in most cases where the disease has proved unresponsive to conventional immunosuppressive therapy, a bone marrow transplant can be a successful treatment [15, 16]. It is now possible to identify such primary genetic defects of gut mucosal integrity in early infancy and treat with stem cell transplant [17].

Current nutritional management of patients undergoing gastroenterological stem cell transplantation is similar to that of post graft versus host disease (GvHD) (p. 340) . Post-transplant, patients are usually maintained on a milk, egg, wheat and soya free diet for up to 2 years. Extreme caution should be applied when challenging with new feeds or foods.

Defects in phagocytes

Phagocytic cells, including macrophages, neutrophils and monocytes, are important in host defence against pyogenic bacteria and other intracellular organisms. These cells leave the bone marrow and migrate to peripheral tissues, particularly at sites of infection or inflammation. Phagocytes ingest pathogens and degrade them; therefore phagocyte defects can lead to severe infection and as a result may be fatal [1]. Some patients may present with gastrointestinal complications similar to those of inflammatory bowel disease [18]. The clinical presentations of some phagocyte defects are

  • chronic granulomatous disease (CGD) where phagocytes cannot produce superoxide radical so cannot degrade pathogens after ingestion
  • deficiencies in any stage of the migration, adherence or transmigration of leucocytes where the finding and destruction of pathogens at the site of an infection is prevented

Children with CGD present with frequent infections, such as pneumonia, which are difficult to cure. These frequent infections increase nutritional requirements and decrease the appetite for food and tolerance of adequate volumes of oral feeds. It is therefore often necessary to initiate enteral feeding as soon as an acute episode begins to prevent excessive weight loss. Energy dense feeds are often tolerated. Diarrhoea is usually common due to intensive antibiotic therapy. Patients may be treated with stem cell transplantation.

Combined immunodeficiencies

Wiskott–Aldrich syndrome

Wiskott–Aldrich syndrome (WAS) is an X-linked immunodeficiency syndrome causing small platelet size. These platelets are mopped up by the spleen with a resultant thrombocytopenia. Immunoglobulin concentrations, T cells and antibody production are also affected [1]. Patients have numerous chronic infections due to reduced immunity, early infantile eczema and they often bleed easily, including bloody diarrhoea. This bleeding results in anaemia which needs to be corrected with iron supplements. Some children may benefit from amino acid based formulas (p. 114) .

Severe combined immune deficiency

Infants with combined immune deficiency, including SCID, have a gene mutation characterised by deficiencies of one or more of the three main lymphocyte subsets (T, B and NK cells). The condition is fatal if untreated. Infants may present at birth or after 3 months of age once maternal immunoglobulin protection has worn off. Infants often present with recurrent severe infections which may be bacterial, fungal or viral. These infections often persist despite treatment [1, 2].

Dietetic management of infants with SCID

Infants diagnosed with SCID often face a nutritional challenge. They may suffer from diarrhoea, malabsorption, vomiting, gastro-oesophageal reflux [19], respiratory infections and/or faltering growth despite a seemingly adequate oral intake. Barron et al. have shown that some of their population of infants with SCID have increased nutritional requirements as a result of hypermetabolism [20]; 100% of the infants presenting with diarrhoea, independent of pneumonia, were at risk of hypermetabolism and subsequent faltering growth. Infants with a diagnosis made between 3 and 12 months of age were at greatest risk.

The use of an energy dense formula, e.g. 0.9 kcal (3.8 kJ)/mL or 1 kcal (4 kJ)/mL, given orally and/or via a nasogastric tube can be indicated, if tolerated. A nasojejunal tube can be considered in infants with ongoing gastro-oesophageal reflux or delayed gastric emptying that is preventing the establishment of oral or nasogastric feeding.

Infants with adenosine deaminase (ADA) deficient SCID often display faltering growth. Once a diagnosis has been made, polyethylene glycol–adenosine deaminase (PEG-ADA) enzyme replacement can be given which may temporarily restore some immune function, thus improving nutritional status.

Parenteral hydration and nutrition may be necessary where an infant requires stabilisation pre or post diagnosis. Some infants with very high requirements may require parenteral nutrition (PN) alongside enteral and/or oral feeds. It may not be possible to meet full requirements with PN alone. Sodium status (urinary and serum) can be a useful tool to ensure adequate sodium levels for growth [21]. In practice, a urinary sodium level <20 mmol/L may indicate poor sodium status (despite normal serum sodium), and sodium supplements may be necessary or the sodium content of PN increased in increments of 1 mmol/kg/day. Urinary sodium levels should then be monitored weekly or biweekly until a level >20 mmol/L is maintained. There is limited evidence for this practice, but clinically this can be effective, especially for infants with chronic diarrhoea who may have high sodium losses. Where full PN is given (except at times of complete gut rest) trophic feeds should be given to help maintain the integrity of the gut mucosa.

Reintroduction of feeds following period of gut rest

At all times reintroduction of enteral feeds should be considered a priority and started as soon as the infant is medically stable. Oral rehydration solution may be given first; if this is tolerated then a suitable formula feed can be introduced. Reintroduction of feeds should be done slowly, often in 1 mL increments as tolerated. Continuous feeding over 20–24 hours is recommended to begin with. Extensively hydrolysed protein formulas (p. 113) or amino acid based formulas (p. 114) are likely to be better tolerated than a whole protein formula. These formulas have higher osmolality than standard formulas; therefore it may be beneficial to start with half standard concentration, building up concentration gradually at 1%–2% at a time. Once standard concentration is achieved and tolerated, it is often necessary to increase the concentration further to achieve higher energy and nutrient density. This should be done with caution, increasing by 1% at a time, usually not exceeding a concentration of 1 kcal/mL (4 kJ/mL). It is often possible to offer the infant a proportion of their feed (however small) orally. This will help to promote oromotor skills, avoid oral sensitisation and can also be a valuable input to the infant’s care by the parent(s).

In older children or infants of weaning age, food can be introduced as early as tolerated. Initially, the diet may be milk, egg, wheat and soya free. This is usually necessary following bone marrow transplant for autoimmune enteropathy and in patients who have developed GvHD post transplant. In addition, foods may be kept ‘bland’, with introduction of one new food at a time. Once immune function has stabilised following transplant, and in the absence of gastrointestinal symptoms, restricted foods can be added in one by one.

Treatment for SCID

Treatment for SCID is primarily haematopoietic stem cell transplantation (HSCT), or more recently by ex vivo gene therapy. Gene therapy may be useful when a well matched donor is not available for HSCT. Stem cells are extracted from the patient, a working copy of the gene is then inserted by retrovirus carrier and the cells are then returned to the patient. Both gene therapy and HSCT are potentially curative and have been proved successful in many patients [22].

Nutritional status may be compromised if chemotherapy such as Melphalan is given for conditioning prior to gene therapy treatment. Dietetic management is similar to that outlined for HSCT (p. 341) .

Haematopoietic stem cell transplantation

In this treatment donor haematopoietic stem cells, usually derived from bone marrow, umbilical cord blood or peripheral blood stem cells, are transplanted into the patient. HSCT remains a risky procedure; however, for patients with SCID or autoimmune enteropathy HSCT can be an effective cure. Transplantation of SCID patients from a matched sibling donor has 90% 3 year survival rate, with mismatched transplants having a 65% success rate [23]. Regardless of diagnosis prior to transplant, maintaining nutritional status pre, peri and post transplant is essential and significantly affects clinical outcome [16, 24]. Energy requirements can be estimated and Schofield equations for predicting resting energy expenditure in children pre transplant have been shown to be suitable [16].

Children receiving an allogeneic haematopoietic stem cell transplant are given myeloablative immunosuppressive conditioning drugs for about 10 days prior to transplant depending on the individual protocol planned for each child. During this time, gut rest is often initiated and PN started, if not already being given.

Reduced intensive conditioning transplant can be used in some SCID patients. This is used where possible due to fewer side effects compared with standard HSCT. This type of transplant may be used where there is a good, matched sibling donor.

When children have coexisting organ damage myeloablative conditioning therapy has been associated with increased treatment toxicity and morbidity. Low intensity conditioning regimens have been shown to be as effective in promoting engraftment and donor immune reconstitution, with minimal toxicity and improved survival.

Infection remains life threatening to children having HSCT and all patients are treated in a reverse isolation unit with high efficiency particulate air filter. Meals may be provided by a designated ward or diet kitchen, or main hospital menus may be adapted following ‘clean’ precautions to reduce the risk of infection from food borne microorganisms (p. 30) . Oral and enteral feeds may be pasteurised as an additional precaution. Some centres may allow commercial bottled water to be taken orally; however, common practice is to only allow water that has been boiled, whether tap or bottled water. Pharmacy grade sterile water can be used, but is often unpalatable. Food restrictions usually continue for 3–6 months post transplant or longer if diagnosed with GvHD.

Complications following HSCT leading to impaired nutritional status


Mucositis is inflammation and/or ulceration of the mucous membranes. This may be present throughout the digestive tract but is most commonly in the mouth making eating or passing a nasogastric tube painful. It is often treated with gut rest.

Graft versus host disease

Graft versus host disease (GvHD) may be present in the mucosa, liver, lungs or skin. GvHD of the gut results in profuse watery diarrhoea, exacerbated by feed/food with a concurrent rapid decline in nutritional status [25]. GvHD is treated with gut rest and/or steroids in severe cases; therefore PN is often needed during this time.

Continuous, low volume amino acid based formula can be initiated once stool frequency has decreased. In severe cases it may be necessary to start with half strength feeds to reduce osmotic load. In some patients, feeds are not tolerated and instead a simple ‘few foods’ diet, e.g. plain chicken with potato or rice, may be gradually reintroduced. Some patients tolerate feed or food better than others, with no known explanation. Oral diet often starts as milk, egg, wheat and soya free, with the later introductions of these foods sequentially once the child is medically stable.

Venous occlusion disease

Venous occlusion disease (VOD) is a condition where the tiny blood veins in the liver become blocked as a result of chemotherapy. Whilst PN has been the preferred method of nutritional support post transplant, especially during times of gut rest, enteral feeding can be used successfully [26]. Almost all patients will require PN for a period of time if they develop severe gut problems.

If VOD is suspected, fluid restriction is indicated and lipid free PN may be necessary. The evidence base for this practice is lacking. Some patients are at higher risk of VOD than others, depending upon their conditioning regimen. It is important to monitor the situation and restart lipids as soon as possible. Lipid free PN is unlikely to meet energy requirements, particularly as resting energy expenditure may be increased [16]. Supplementation with walnut oil (p. 601) to meet essential fatty acid requirements should be considered early on, particularly if lipid free PN is used for prolonged periods, or if the patient is a young infant.

Dietetic management of HSCT

A suggested protocol is to pass a nasogastric tube prior to the start of conditioning, i.e. day 5 HSCT (day 0 is when the stem cell infusion is given), before mucositis may develop. Passing a nasogastric tube when the patient already has severe mucositis may be very traumatic.

Dietetic management of HSCT is similar to that described for SCID patients. Hydrolysed protein formulas are usually better tolerated post transplant than whole protein formulas. Patients may initially require a continuous feeding regimen, building up to an overnight feed, daytime boluses and oral diet. A normal ‘clean’ diet, including cow’s milk protein, is usually tolerated and can be encouraged. Oral intake is often slow to recover to achieve full nutritional requirements, so some children may require enteral feeds for several months after discharge from hospital.

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Apr 1, 2017 | Posted by in NUTRITION | Comments Off on Immunodeficiency Syndromes, HIV and AIDS: Immunodeficiency Syndromes

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