There are 2 types of immunoglobulins

• Normal (nonspecific) - from unselected donors
• Hyperimmune (specific) - from selected donors

Side-effects of both types

• Malaise, chills, fever
• Headache, nausea, facial flushing
• Anaphylaxis (rarely)

Human normal immunoglobulin

Human normal immunoglobulin (HNIG) is made from the plasma of about 1,000 donors. This provides antibodies against hepatitis A, rubella, measles and other viruses prevalent in the general population. It is most effective within 3 days of contact (but has some effect up to 6 days); protection is immediate and lasts several weeks. They block the immune response to live vaccines (except yellow fever) for 3 months, and live vaccines should ideally be given at least 3 weeks before or 3 months after an injection of HNIG, although this can be ignored if there is insufficient time, eg for travellers. It is contra-indicated in those with class-specific antibody to IgA.

HNIG is used for:

• Hepatitis A contact in immunocompromised patients, preferably given within 72 hours, together with hepatitis A vaccine (HAV) - in a different site because there may be a poor antibody response to the vaccine alone. HAV vaccine protects normal individuals if given within a week of contact (possibly even up to the day of travel).^[2]
• Rubella contact in nonimmune pregnant women where termination is unacceptable^[3] - it does not prevent infection but reduces symptoms and the risks to the fetus. Give as soon as possible after exposure. Serological follow-up is essential. Measles, mumps and rubella (MMR) and anti-D may be given in the postpartum period (separate syringes and into different limbs). Measure rubella antibodies after 8 weeks and vaccinate if necessary. However, rubella vaccine is not effective for post-exposure prophylaxis.
• Measles contact, within 72 hours of exposure (some effect if given within 6 days) if:^[4]
  • Immunocompromised
  • Nonimmune pregnant women (but no evidence it prevents fetal loss)
  • Infant under 9 months - if mother not immune
  • Infant 6-8 months - if mother immune (because under 6 months the child is protected by maternal antibodies and after 9 months MMR can be given for prophylaxis following exposure to measles)
• Poliomyelitis - HNIG may reduce the risk of developing paralysis in the immunocompromised but there is no evidence to support this^[5]

Intravenous HNIG is also used to give broad-spectrum passive protection to premature babies, patients with congenital hypogammaglobulinaemia, immunoglobulin deficiencies, autoimmune disorders, eg thrombocytopenic purpura (where temporary, rapid rise in platelets is needed, such as pregnancy, or preoperatively), Kawasaki syndrome, following bone-marrow transplantation, children with HIV, Guillain-Barré syndrome, and myasthenia gravis (unlicensed use) when it can induce remission in severe relapse.

Note: for mumps contacts, neither HNIG nor MMR offer protection.

Human specific immunoglobulins

• Hepatitis B immunoglobulin^[6][7] (see separate article Hepatitis B Vaccination and Prevention) is used after needlestick or sexual exposure and in infants born to infected mothers (persistent carrier with detectable hepatitis e antigen or its antibody or in recent infection). It should also be given in hepatitis B mothers when the birth weight of the baby is <1500 g. The sexual contacts of acute hepatitis B sufferers and chronic hepatitis B sufferers (newly diagnosed) should also receive specific immunoglobulin if unprotected sexual contact occurred in the previous seven days. It should be given preferably within 12 hours and not later than 1 week after exposure. Hepatitis B vaccine should also be given.
• Human varicella-zoster immunoglobulin is given to the nonimmune exposed to chickenpox or shingles if at risk of severe infection:^[8]
  • Immunocompromised individuals
  • High-dose steroidal therapy (adult who has received 40 mg daily for more than a week in the previous 3 months, or a child who has received a daily dose of 2 mg/kg for more than a week, or 1 mg/kg for more than a month, in the previous 3 months)
  • Nonimmune pregnant women (to protect the fetus)
  • Neonates of women who develop chickenpox 7 days before/after delivery
  • Significant exposure to the virus
• Rabies immune globulin^[9] is indicated for an unimmunised person exposed to a bite from an animal from a high-risk country; as much as possible is injected into or around the cleansed wound (after washing with soapy water). Rabies vaccine should also be given.
• Tetanus immunoglobulin^[10] (together with metronidazole and wound cleansing) is given for tetanus-prone wounds, in the nonimmune or those not up-to-date with boosters. Tetanus vaccine should also be given. IV immunoglobulins are also given for treatment of tetanus).
• Cytomegalovirus immune globulin (on a named-patient basis) for patients receiving immunosuppressive treatment.

Rarer uses of immunoglobulins

• Aplastic anaemia - IV antilymphocytic globulin (50% respond).
• Diphtheria anti-toxin - (from horses) for suspected diphtheria, adverse reactions are common. Diphtheria antitoxin does not provide any benefit when used prophylactically.^[11]
• Botulism antitoxin for suspected botulism; again, adverse reactions are common.

Availability

Immunoglobulins are available from NHS microbiology laboratories and, in Scotland, from the Blood Transfusion Service - they are prepared by Bio Products Laboratory (BPL), and are issued by the Health Protection Agency.