IgG Index, IgG Synthesis Rate, IgG(loc) and IgGPROD
Gautam Thor, Ph.D.

Qalb(the ratio of CSF Albumin/Serum Albumin) gives an approximation of the permeability of the blood-CSF barrier, with Qalb×103 values >9 being considered abnormal. By division of the CSF/serum quotient of an immunoglobulin (IgG, IgA or IgM) by the CSF/serum quotient of albumin gives an approximation between brain-derived (intrathecal) and blood-derived immunoglobulin fractions is obtained; this approximation reflects the physiological principles that govern the transduction of albumin and immunoglobulins across the blood-CSF barrier.2

IgG Index = IgG(CSF)/IgG(Serum) ÷ Albumin(Serum)/Albumin(CSF)

There are several empirical formulae that use similar quotients to obtain a measure of increased intrathecal synthesis of IgG including IgG synthesis rate,3 IgG(loc),4 which defines the minimum amount of local IgG synthesis, and IgGPROD.5

IgGPROD5 (mg/L) = CSF IgG – [10.51 × CSF Alb × Serum IgG/Serum Alb]

Unlike the IgG index, which is unitless, the IgGPROD and IgG(loc) measure intrathecal IgG production in mg per liter CSF and are particularly beneficial when serial determinations from the same patient are performed.

A comparison of these and other equations suggests that in cases of blood-brain barrier damage, IgG index and IgGPROD have the optimum clinical utility in evaluating multiple sclerosis cases.6,7 A significant decrease in the IgG index for cyclophosphamide-treated MS patients can be observed.8

The combined use of IgG index and IgG(loc) provides accurate quantitation of intrathecal IgG synthesis and is as sensitive (92%) as the qualitative detection (96%) of oligoclonal bands in MS.6,9 The IgG synthesis rate for patients with tuberculosis meningitis is higher than that of patients with aseptic meningitis (AM), leading to a 100% sensitivity and a 83.3% specificity in terms of the distinction between the two.10 With the Reiber formula4 for Ig(loc) to calculate the synthesis of total intrathecal immunoglobulins; 85% (40/47) of patients with neuroborreliosis and 55% (22/40) of patients with viral meningoencephalitis11 had intrathecal autoantibodies (IgG, IgM and/or IgA) to neuronal proteins. Compared to paired serum samples, the perilymph from 7 patients with Meniere disease had higher HSV-specific IgG indices12 but unaltered indices for cytomegalovirus, Epstein-Barr virus or measles virus. Diagnosis of herpes simplex virus encephalitis is >80% sensitive when measured by day 11 of disease onset;13 the same sensitivity is achieved with combined indirect EIA and immunoblotting techniques to detect HSV-1 IgG synthesis in the CNS.14


Relevant Tests Offered by GBMC
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REFERENCES

  1. Mattila KM, Pirttila T, Blennow K, et al. Altered blood-brain barrier function in Alzheimer's disease? Acta Neurol Scand 1994;89:192-8.
  2. Reiber H. External quality assessment in clinical neurochemistry: survey of analysis for cerebrospinal fluid (CSF) proteins based on CSF/serum quotients. Clin Chem 1995;41:256-63.
  3. Tourtellotte WW, Potvin AR, Fleming JO, et al. Multiple sclerosis: measurement and validation of central nervous system IgG synthesis rate. Neurology 1980;30:240-4.
  4. Reiber H, Felgenhauer K. Protein transfer at the blood cerebrospinal fluid barrier and the quantitation of the humoral immune response within the central nervous system. Clin Chim Acta 1987;163:319-28.
  5. Blennow K, Fredman P, Wallin A, et al. Protein analyses in cerebrospinal fluid. II. Reference values derived from healthy individuals 18-88 years of age. Eur Neurol 1993;33:129-33.
  6. Blennow K, Fredman P, Wallin A, et al. Formulas for the quantitation of intrathecal IgG production. Their validity in the presence of blood-brain barrier damage and their utility in multiple sclerosis. J Neurol Sci 1994;121:90-6.
  7. McMillan SA, Douglas JP, Droogan AG, Hawkins SA. Evaluation of formulae for CSF IgG synthesis using data obtained from two methods: importance of receiver operator characteristic curve analysis. J Clin Pathol 1996;49:24-8.
  8. Salmaggi A, Milanese C, Eoli M, La Mantia L, Nespolo A, Dufour A. Immunological monitoring and clinical evaluation in cyclophosphamide-treated progressive multiple sclerosis patients. Intern J Neurosci 1994;76:305-12.
  9. Peter JB, Bowman RL. Intra-blood-brain barrier synthesis of IgG: Comparison of IgG synthesis formulas in a computer model and in 1,629 consecutive specimens. Neurology 1992;42:510-5.
  10. Cho TY, Park SC, Cho SN, et al. Intrathecal synthesis of immunoglobulin G and mycobacterium tuberculosis-specific humoral immune response in tuberculous meningitis. Clin Diagn Lab Immunol 1995;2:361-4.
  11. Kaiser R. Intrathecal immune response in patients with neuroborreliosis: specificity of antibodies for neuronal proteins. J Neurol 1995;242:319-25.
  12. Arnold W, Niedermeyer HP. Herpes simplex virus antibodies in the perilymph of patients with Meniere disease. Arch Otolaryngol Head Neck Surg 1997;123:53-7.
  13. Skoldenberg B. Herpes simplex encephalitis. Scand J Infect Dis 1991;80(Suppl):40-6.
  14. Markoulatos P, Labropoulou V, Kordossi A, Krikelis V, Spyrou N, Moncany MLJ. A combined indirect ELISA and immunoblotting for the detection of intrathecal herpes simplex virus IgG antibody synthesis in patients with herpes simplex virus encephalitis. J Clin Lab Anal 1995;9:325-33.