Question 1

What is the difference between polyclonal and monoclonal gammopathy on SPEP?

Accepted Answer

Polyclonal gammopathy appears as a broad, diffuse elevation of the gamma fraction on SPEP, reflecting increased production from many plasma cell clones (typical of chronic infection, autoimmune disease, or liver disease). Monoclonal gammopathy appears as a sharp, narrow peak (M-spike), representing overproduction from a single plasma cell clone (typical of MGUS, multiple myeloma, Waldenström macroglobulinaemia).

Question 2

What immunoglobulins are affected in common variable immunodeficiency?

Accepted Answer

CVID typically shows low IgG (mandatory) plus low IgA and/or low IgM. Age at diagnosis is usually 20–40 years. All patients with low IgG and low IgA should be referred to clinical immunology for further assessment, including specific antibody responses and exclusion of secondary causes (protein-losing enteropathy, drugs (including rituximab, corticosteroids, anticonvulsants), nephrotic syndrome).

Question 3

What is IgG4-related disease and how is it diagnosed?

Accepted Answer

IgG4-RD is a fibroinflammatory condition characterised by elevated serum IgG4 (>135 mg/dL) and IgG4/IgG ratio >8% in about 70% of patients. Classic presentations include: autoimmune pancreatitis, sialadenitis, orbital pseudotumour, retroperitoneal fibrosis, and tubulointerstitial nephritis. Serum IgG4 is not diagnostic alone — tissue biopsy showing lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis is required for definitive diagnosis.

Question 4

Can drug therapy affect immunoglobulin levels?

Accepted Answer

Yes — several medications can alter immunoglobulin levels: rituximab (depletes B-cells → IgG/IgA/IgM may fall over 6–12 months), corticosteroids (modest reduction of IgG), anticonvulsants (phenytoin, carbamazepine → IgA deficiency), immunosuppressants (mycophenolate → variable reduction), and chemotherapy. Always review the medication list when interpreting low immunoglobulins.