CSF IgG Synthesis Rate Calculator (Tourtellotte)
CSF IgG Synthesis Rate Calculator (Tourtellotte)
The Tourtellotte formula for daily intrathecal IgG production, in mg per 24 hours. All four inputs must be in the same units the formula was derived in — so the units are an input here rather than a footnote.
CSF IgG Synthesis Rate (Tourtellotte)
IgG + albumin, CSF and serum → mg/dayCSF IgG 8.5 mg/dL, CSF albumin 28 mg/dL, serum IgG 1,150 mg/dL, serum albumin 4,200 mg/dL
The Tourtellotte formula
All four concentrations in mg/dL. Reference interval −9.9 to +3.3 mg/24 h.
- 369
- the normal serum:CSF IgG ratio. IgG_serum ÷ 369 is the CSF IgG that passive transfer alone would produce in a person with an intact barrier, and subtracting it leaves the excess
- 230
- the normal serum:CSF albumin ratio. Albumin is made only in the liver, so any CSF albumin above Alb_serum ÷ 230 measures how leaky the blood–CSF barrier is — this term is the barrier correction
- 0.43
- the molecular-size correction, the ratio of the molecular weights of albumin (about 69 kDa) to IgG (about 160 kDa). A leaking barrier lets the smaller albumin through more readily than IgG, so the excess albumin has to be scaled down before it is used to predict excess IgG
- 5
- the volume of CSF produced each day — 500 mL, expressed as 5 decilitres. This is what converts a concentration in mg/dL into a production rate in mg/day, and it is why every input must be in mg/dL rather than mg/L or g/L
- negative results are normal
- two modelled quantities are subtracted from one measured one, so a person with no intrathecal synthesis frequently lands below zero. The published interval starts at −9.9 mg/24 h
Worked example
CSF IgG 8.5 mg/dL, CSF albumin 28 mg/dL, serum IgG 1,150 mg/dL, serum albumin 4,200 mg/dL
Passive IgG transfer = 1,150 ÷ 369 = 3.12 mg/dL, so the excess CSF IgG is 8.5 − 3.12 = 5.38 mg/dL
Passive albumin transfer = 4,200 ÷ 230 = 18.26 mg/dL, so the excess CSF albumin is 28 − 18.26 = 9.74 mg/dL — the barrier is mildly leaky
Scale that leak into the IgG it would explain: 9.74 × (1,150 ÷ 4,200) × 0.43 = 9.74 × 0.2738 × 0.43 = 1.15 mg/dL
Excess not explained by the leak = 5.38 − 1.15 = 4.24 mg/dL, and over 5 dL of CSF a day that is 4.24 × 5 = 21.2 mg/day
21.2 is well above the upper reference limit of 3.3 mg/24 h, so IgG is being synthesised inside the central nervous system
Note how much work the barrier term did: without it the answer would have been 5.38 × 5 = 26.9 mg/day. Skipping the albumin correction overstates synthesis in every patient whose barrier is leaking, which is most of the ones being investigated
Getting the units right before the formula is applied
| Result | Usual UK/European report | Multiply by | Value the formula needs |
|---|---|---|---|
| CSF IgG | mg/L — e.g. 85 mg/L | ÷ 10 | 8.5 mg/dL |
| CSF albumin | mg/L — e.g. 280 mg/L | ÷ 10 | 28 mg/dL |
| Serum IgG | g/L — e.g. 11.5 g/L | × 100 | 1,150 mg/dL |
| Serum albumin | g/L — e.g. 42 g/L | × 100 | 4,200 mg/dL |
The three ways of measuring intrathecal IgG, compared
| Test | What it reports | Corrects for barrier leak? | Where it stands |
|---|---|---|---|
| Oligoclonal bands by isoelectric focusing | Bands present in CSF and not in paired serum | Not needed — qualitative, and paired serum excludes systemic bands | The reference method. More sensitive than any quotient and the standard against which they are judged |
| IgG index | (IgGCSF/IgGserum) ÷ (AlbCSF/Albserum), unitless, abnormal above about 0.7 | Yes, as a ratio of ratios | The most widely used quantitative measure; simple, unit-independent, no molecular-size term |
| IgG synthesis rate (Tourtellotte) | mg of IgG made per 24 hours | Yes, with an explicit molecular-size correction | Physiologically the most explicit, and the most unit-sensitive. Adds little to the index in routine practice |
A production rate, not a ratio
The IgG index answers whether immunoglobulin is being made inside the central nervous system with a unitless ratio of ratios. The Tourtellotte formula answers the same question with a number that has physical meaning: milligrams of IgG synthesised per day. It gets there by subtracting two things from the measured CSF IgG. The first is the IgG that would have crossed an intact blood–CSF barrier anyway, taken as the serum IgG divided by 369, the normal serum:CSF ratio. The second is the extra IgG explained by a leaking barrier, worked out from the excess CSF albumin — albumin is made only in the liver, so all of it in the CSF arrived by transfer — scaled by the patient’s own serum IgG:albumin ratio and then by 0.43, the ratio of the molecular weights of albumin and IgG, because a leak passes the smaller molecule more readily. What survives both subtractions is multiplied by 5, the number of decilitres of cerebrospinal fluid produced in a day.
That last coefficient is why this page asks for units before it asks for anything else. The 369 and the 230 are dimensionless and would survive any unit you cared to use. The 5 would not: it is 500 mL expressed in decilitres, so the bracket in front of it has to be in mg/dL for the answer to come out in mg/day. A UK laboratory reports CSF IgG and CSF albumin in mg/L and both serum proteins in g/L, which is three units across four numbers and none of them the one the formula wants. A hundredfold error in the serum pair is easy to make and almost impossible to spot afterwards, because the result is a small signed number whichever way it goes.
Negative results are normal and should not be reported as errors. The published reference interval runs from −9.9 to +3.3 mg per 24 hours, and it starts below zero because two modelled quantities are being subtracted from one measured one; in a person with no intrathecal synthesis the subtraction routinely overshoots. A negative answer means none was detected.
A raised synthesis rate is a finding and not a diagnosis. It occurs in multiple sclerosis and just as readily in neurosyphilis, Lyme neuroborreliosis, subacute sclerosing panencephalitis, HIV, neurosarcoidosis, lupus with central nervous system involvement and chronic meningitis. It is also less sensitive than isoelectric focusing for oligoclonal bands, which remains the reference method and is what current diagnostic criteria rely on; roughly 5 to 10 per cent of people with clinically definite multiple sclerosis have no detectable intrathecal synthesis by any method. And every quotient-based formula, this one included, becomes unreliable as the barrier breaks down, because the correction it applies is a linear model of a relationship that is not linear at high permeability. The number supports the clinician’s judgement about what the CSF is showing; it does not make the diagnosis.
Frequently asked questions
What is a normal CSF IgG synthesis rate?
The published reference interval is −9.9 to +3.3 mg per 24 hours, so anything at or below 3.3 mg/day is normal. Negative values are expected rather than erroneous: the formula subtracts two modelled correction terms from one measured concentration, and in a person with no intrathecal synthesis that subtraction routinely overshoots zero.
Why does the Tourtellotte formula need mg/dL?
Because two of its coefficients are unit-bound. The 0.43 is a molecular-weight ratio and the 5 is the daily CSF volume of 500 mL expressed in decilitres, so the bracket must be in mg/dL for the answer to come out in mg/day. Reports in mg/L and g/L must be converted first, which this page does for you once you state the units.
Is the synthesis rate better than the IgG index?
Not in routine practice. They answer the same question and usually agree, and the index is unitless, simpler and harder to get wrong. The synthesis rate is more explicit physiologically — it names a production rate in mg per day and applies a molecular-size correction — but it adds little diagnostic information over the index.
Does a raised IgG synthesis rate mean multiple sclerosis?
No. It means IgG is being produced inside the central nervous system, which happens in neurosyphilis, Lyme neuroborreliosis, subacute sclerosing panencephalitis, HIV, neurosarcoidosis, lupus with CNS involvement and chronic meningitis as well as in multiple sclerosis. Isoelectric focusing for oligoclonal bands on paired CSF and serum is the confirmatory test.
What if the blood–CSF barrier is damaged?
Interpret the result cautiously. The albumin term corrects for barrier leak using a linear model, and that model stops holding when permeability is high — a markedly raised albumin quotient makes every quotient-based formula less reliable. Isoelectric focusing does not depend on the barrier model and is the better test in that situation.
Related calculators
References
- Tourtellotte WW, Potvin AR, Fleming JO, et al. Multiple sclerosis: measurement and validation of central nervous system IgG synthesis rate. Neurology. 1980;30(3):240–244.
- Laboratory Corporation of America. Test 085928 — Immunoglobulin G Synthesis Rate, Cerebrospinal Fluid: calculation and reference interval (−9.9 to +3.3 mg/24 hours). Labcorp test directory.
- Lefvert AK, Link H. IgG production within the central nervous system: a critical review of proposed formulae. Ann Neurol. 1985;17(1):13–20.
- Freedman MS, Thompson EJ, Deisenhammer F, et al. Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis: a consensus statement. Arch Neurol. 2005;62(6):865–870.
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