Calculated globulin (CG) as a screening test for antibody deficiency

Abstract

SummaryCalculated globulin (total protein – albumin) is usually tested as part of a liver function test profile in both primary and secondary care and determines the serum globulin concentration, of which immunoglobulins are a major component. The main use hitherto of calculated globulin is to detect paraproteins when the level is high. This study investigated the potential to use low levels of calculated globulin to detect antibody deficiency. Serum samples with calculated globulin cut-off < 18 g/l based on results of a pilot study were collected from nine hospitals in Wales over a 12-month period. Anonymized request information was obtained and the samples tested for immunoglobulin levels, serum electrophoresis and, if appropriate, immunofixation. A method comparison for albumin measurement using bromocresol green and bromocresol purple was undertaken. Eighty-nine per cent (737 of 826) samples had an immunoglobulin (Ig)G level of < 6 g/l using the bromocresol green methodology with a cut-off of < 18 g/l, and 56% (459) had an IgG of < 4 g/l. Patients with both secondary and primary antibody deficiency were discovered and serum electrophoresis and immunofixation showed that 1·2% (10) had previously undetected small paraproteins associated with immune-paresis. Using bromocresol purple, 74% of samples had an IgG of < 6 g/l using a cut-off of < 23 g/l. Screening using calculated globulin with defined cut-off values detects both primary and secondary antibody deficiency and new paraproteins associated with immune-paresis. It is cheap, widely available and under-utilized. Antibody-deficient patients have been discovered using information from calculated globulin values, shortening diagnostic delay and time to treatment with immunoglobulin replacement therapy.

Propensity‐Score Matched Comparative Study on Effects of Intravenous Human Serum Albumin Administration in Critically Ill Adult Patients Receiving Parenteral Nutrition

“…The clinical consequences of these findings remain unknown because we did not study which NAPP were affected. However, the main component of NAAP are globulins, and low globulins have been linked to an antibody deficiency . Alternatively, other important plasma proteins, such as fibrinogen, α‐2‐macroglobulin, plasminogen, or ceruloplasmin could be decreased.…”

“…However, the main component of NAAP are globulins, and low globulins have been linked to an antibody deficiency. 24 Alternatively, other important plasma proteins, such as fibrinogen, α-2-macroglobulin, plasminogen, or ceruloplasmin could be decreased. The rest of the nutrition variables were not altered by the IV HSA administration in our study.…”

Antibody deficiency in patients taking clozapine

“…Various mechanisms have been proposed for the rise in pneumonia, including sedation, sialorrhoea and aspiration, agranulocytosis, and smoking 910. Following the introduction of calculated globulin screening in Wales,11 we found a novel and striking association between use of the antipsychotic clozapine and antibody deficiency 12. Patients taking clozapine follow an intensive regimen of blood testing for the rare risk of agranulocytosis (with cumulative incidence of <1% cases), but antibody testing is not included in existing clozapine monitoring programmes.…”

Low plasma viscosity as an indicator of antibody deficiency

“…1 Delayed diagnosis is linked to significant and avoidable risk of bronchiectasis. Serendipitous laboratory clues pointing to antibodyrelated immunodeficiency include IgA deficiency in coeliac disease testing, 2 low IgE in allergy testing 3 and low calculated globulin (total protein minus the albumin concentration 4,5 ). A prolonged acute phase response elevates plasma viscosity (PV), and this assay is used primarily as a nonspecific marker of inflammation.…”