Antibody replacement therapy in primary antibody deficiencies and iatrogenic hypogammaglobulinemia

Abstract

Antibody replacement therapy has been used in the treatment of primary antibody deficiencies (PADs) for several decades, and an evidence-based guideline for its treatment is currently available. By contrast, the use of antibody replacement therapy in iatrogenic hypogammaglobulinemia (IHG), a condition that is associated with immunosuppressive medication, has hardly any evidence base and no guidelines. As IHG can be equally as severe as PAD and is much more prevalent, evidence-based guidelines are urgently needed. This review will focus on the differences and similarities between PAD and IHG and the use of antibody replacement therapy in both conditions. Suggestions for the development of evidence-based guidelines and future research are given.

Keywords:

• antibody replacement therapy
• iatrogenic hypogammaglobulinemia
• immunodeficiency
• immunoglobulin
• primary antibody deficiency

Financial & competing interest’s disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

• The pathogenesis of primary antibody deficiency (PAD) is based on defects at various stages of B-cell development. Immunosuppressive therapies can suppress B-cell development at various stages and can thereby cause iatrogenic hypogammaglobulinemia (IHG).

• The clinical and laboratory manifestations of both PAD and IHG comprise a broad spectrum and vary between the type of PAD or IHG and even between patients with the same type of immune deficiency.

• The most common clinical features are recurrent bacterial respiratory tract infections, but also viral and fungal infections.

• Substitution treatment with intravenous or subcutaneous immunoglobulins can decrease the infection frequency and improve the quality of life in PAD patients.

• The evidence base for the use of antibody replacement therapy in IHG is limited compared to that in PAD. Based on that limited evidence, antibody replacement therapy seems to be effective in reducing the infection frequency in IHG patients.

• Routine measurement of immunoglobulin levels is advised before and during immunosuppressive therapy.

• Antibody replacement therapy in IHG differs from that in PAD in that the development of IHG can be monitored and that antibody replacement therapy can be started before a patient presents with severe infections and possibly organ damage.

• The best time of cessation of antibody replacement therapy in IHG is not always clear. This should be after the immunosuppressive therapy is stopped, but in some cases, prolonged substitution treatment may be warranted.

• Before the start of antibody replacement therapy, prophylactic antibiotics, vaccination and cessation of immunosuppressive therapy should be considered in the treatment of IHG.

• Some forms of PAD and IHG present with low immunoglobulin levels and an impaired response to vaccination, but no clinical signs of immune deficiency. In these cases, restraint should be exercised in starting antibody replacement therapy.

Notes