Reiber CSF Immunoglobulin Quotient Calculator

Q: What is the Reiber quotient diagram?

A plot of the immunoglobulin quotient against the albumin quotient, with a hyperbolic reference line drawn on it. Points below the line are explained by transfer from blood; points above it indicate immunoglobulin made inside the central nervous system. Because the line curves, the diagram separates barrier dysfunction from local synthesis in a way a single ratio cannot.

Q: How is the intrathecal fraction calculated?

IF% = (1 − QLim ÷ QIg) × 100, where QIg is the measured immunoglobulin quotient and QLim is the hyperbolic limit for that class at the patient's albumin quotient. It expresses how much of the immunoglobulin in the fluid was produced locally. Reiber's manual advises against calling a fraction elevated below 10%, because between-laboratory variation in the four underlying measurements is larger than that.

Q: Why does the IgG index give a different answer?

Because it assumes the relationship between the two quotients is a straight line through the origin and it is not. Expressed as an index, the hyperbolic limit rises from about 0.62 at an albumin quotient of 2×10⁻³ to about 0.85 at 20×10⁻³. A fixed cut-off of 0.7 is therefore too strict when the barrier is tight and far too lenient when it has broken down, which is when it most often gets used.

Q: Which immunoglobulin class should be measured?

All three where the laboratory offers them, because the dominant class is itself diagnostic information. An IgG-dominant response fits multiple sclerosis, neurosyphilis or HIV encephalitis; IgA dominance is described in neurotuberculosis, brain abscess and adrenoleukodystrophy; IgM dominance in Lyme neuroborreliosis, mumps, central nervous system lymphoma and African trypanosomiasis. Measuring IgG alone reduces the test to yes or no.

Q: Is a normal albumin quotient needed for this calculation?

No — the opposite. The hyperbolic limit exists precisely so that the calculation stays valid when the barrier is disturbed, and it moves with the albumin quotient automatically. What the albumin quotient does is tell you whether the barrier is abnormal for the patient's age, using QAlb(ref) < (4 + age÷15) × 10⁻³, and that is reported separately because it is a finding in its own right.

Q: Does a negative intrathecal fraction mean something is wrong?

No. It just means the measured quotient sits below the discrimination line, which is where most samples sit. The number is the signed distance from the line, so it is negative whenever there is no intrathecal synthesis to detect. Report it as none detected rather than as a negative quantity of immunoglobulin.

Reiber’s hyperbolic discrimination line for IgG, IgA and IgM, with the absolute and relative intrathecal synthesis it implies. The relationship between the immunoglobulin quotient and the albumin quotient is a curve, not a straight line — which is why a linear IgG index reads “intrathecal synthesis” on a damaged blood–CSF barrier where there is none.

Last updated 17 Sep 2026

Reiber CSF immunoglobulin quotient

Paired Ig + albumin → intrathecal fraction

Immunoglobulin classEach class has its own hyperbola, because the limit is set by molecular size and IgM is the largest of the three. Choosing the wrong class is the commonest way to get this calculation badly wrong.

CSF immunoglobulin (mg/L)With an intact barrier, CSF IgG is roughly 10–60 mg/L, IgA 1–6 mg/L and IgM 0.1–1 mg/L. Multiply mg/dL by 10. This must be measured on the same sample as the CSF albumin.

Serum immunoglobulin (g/L)Serum IgG is usually 7–16 g/L, IgA 0.7–4 g/L, IgM 0.4–2.3 g/L. Drawn at the same time as the lumbar puncture, or within a day or two of it.

CSF albumin (mg/L)Typically 100–350 mg/L with an intact barrier. This is the term that carries the whole barrier correction, and the one most often entered in the wrong unit.

Serum albumin (g/L)Usually 35–50 g/L. Entering mg/dL here instead of g/L moves the albumin quotient by a factor of 100 and makes the result meaningless rather than merely wrong.

Age (years)Used only for the age-related reference limit on the albumin quotient itself, QAlb(ref) < (4 + age÷15) × 10⁻³. The formula applies above age 5; below that, the barrier is still maturing and the reference range is different again.

25.2% intrathecal fractionExample

IgG; CSF IgG 60 mg/L, serum IgG 11 g/L, CSF albumin 240 mg/L, serum albumin 42 g/L, age 38

Formula

QAlb = CSF albumin ÷ serum albumin QIg = CSF Ig ÷ serum Ig
QLim(Ig) = a · √(QAlb² + b²) − c
IgLoc = (QIg − QLim) × serum Ig IF% = (1 − QLim ÷ QIg) × 100
QAlb(ref) < (4 + age ÷ 15) × 10⁻³

QAlb: the albumin quotient, the measure of blood–CSF barrier function. Albumin is made only in the liver, so all of it in cerebrospinal fluid arrived from blood and none of the quotient is contaminated by local synthesis
a, b, c: class-specific constants set by molecular size. IgG 0.93, 6×10⁻⁶, 1.7×10⁻³; IgA 0.77, 23×10⁻⁶, 3.1×10⁻³; IgM 0.67, 120×10⁻⁶, 7.1×10⁻³. b is quoted here as b² because that is the form the constants are published in
QLim: the discrimination line — the highest immunoglobulin quotient that blood-to-CSF transfer alone can produce at that barrier state. It is the mean plus three standard deviations of a non-inflammatory reference population, and contains 99% of it
IgLoc: absolute intrathecal synthesis in mg/L of cerebrospinal fluid — the distance above the line, converted back into a concentration by multiplying by the serum level
IF%: the intrathecal fraction: how much of the immunoglobulin in the fluid was made locally, as a percentage. Reported here because it is the figure that transfers between laboratories. Reiber’s manual says not to call it elevated below 10%
the hyperbola: as the barrier fails, QAlb rises and the immunoglobulin quotients rise faster, approaching the albumin quotient asymptotically. Fitting that with a straight line through the origin — which is what an index does — is what goes wrong

Worked example

IgG; CSF IgG 60 mg/L, serum IgG 11 g/L, CSF albumin 240 mg/L, serum albumin 42 g/L, age 38
QAlb = 240 ÷ 42,000 = 5.71 × 10⁻³ — within the limit for 38 years, which is (4 + 38÷15) × 10⁻³ = 6.53 × 10⁻³
QIgG = 60 ÷ 11,000 = 5.45 × 10⁻³
QLim(IgG) = 0.93 × √((5.71×10⁻³)² + 6×10⁻⁶) − 1.7×10⁻³ = 4.08 × 10⁻³
QIgG is above the line, so there is intrathecal synthesis
IF% = (1 − 4.08 ÷ 5.45) × 100 = 25.2% of the CSF IgG was made locally
IgLoc = (5.45 − 4.08) × 10⁻³ × 11,000 = 15.1 mg/L in absolute terms
For comparison, the linear IgG index on the same four numbers is 5.45 ÷ 5.71 = 0.95, also positive — the two models agree here because the barrier is intact

The hyperbolic limit, expressed as the IgG index it corresponds to

Third column computed from QLim(IgG) = 0.93√(QAlb² + 6×10⁻⁶) − 1.7×10⁻³. It is the IgG index value that the hyperbolic limit corresponds to at each barrier state — the cut-off a linear index would need in order to mean the same thing. It is not a constant, and that is the entire argument for the curve.
QAlb (×10⁻³)	QLim(IgG) (×10⁻³)	QLim ÷ QAlb	What a fixed IgG index cut-off of 0.7 does at this barrier state
2.0	1.24	0.62	Under-calls. The hyperbolic line was crossed at 0.62, so index values between 0.62 and 0.70 are intrathecal synthesis the index reports as normal
5.0	3.48	0.70	Agrees exactly. This is roughly the barrier state the 0.7 cut-off was derived on, which is why it works as well as it does
6.5	4.76	0.73	Begins to over-call. An index of 0.72 here is below the hyperbolic line — normal transfer through a mildly leaky barrier
10.0	7.87	0.79	Over-calls. Everything from 0.70 to 0.79 is explained by the barrier and not by local synthesis
20.0	17.04	0.85	Over-calls badly. Fifteen index points of apparent intrathecal synthesis that are not there
30.0	26.29	0.88	Not usable. At this degree of barrier breakdown the index is measuring the barrier, not the immune response

The three classes, and what a dominant class suggests

Constants from Reiber’s CSF manual, 2020 edition. The limits fall as molecular size rises because a larger molecule crosses less readily at any given barrier state. Measuring all three classes rather than IgG alone is what turns a yes-or-no answer into a differential — a two- or three-class response is itself a pattern, described in mumps, trypanosomiasis and opportunistic infection.
Class	a	b²	c	QLim at QAlb = 6.5×10⁻³	Dominant-class pattern
IgG	0.93	6×10⁻⁶	1.7×10⁻³	4.76×10⁻³	Multiple sclerosis, neurosyphilis, HIV encephalitis
IgA	0.77	23×10⁻⁶	3.1×10⁻³	3.12×10⁻³	Neurotuberculosis, brain abscess, adrenoleukodystrophy
IgM	0.67	120×10⁻⁶	7.1×10⁻³	1.43×10⁻³	Lyme neuroborreliosis, mumps meningoencephalitis, central nervous system non-Hodgkin lymphoma, African trypanosomiasis

Age-related upper reference limit for the albumin quotient

From QAlb(ref) < (4 + age÷15) × 10⁻³, which applies above about 5 years of age. Reiber's manual also prints a rounded table giving 5, 6.5 and 8 ×10⁻³ at 15, 40 and 60 years; the formula gives 6.7 rather than 6.5 at 40, and the discrepancy is the manual's rounding rather than a second rule. Age is the reason a quotient of 8×10⁻³ is barrier dysfunction in a student and normal in a pensioner.
Age (years)	QAlb upper limit
15	5.0 × 10⁻³
20	5.3 × 10⁻³
30	6.0 × 10⁻³
40	6.7 × 10⁻³
50	7.3 × 10⁻³
60	8.0 × 10⁻³
70	8.7 × 10⁻³

Why the line is a curve, and what that costs the IgG index

Every quantitative test for intrathecal immunoglobulin has to answer one question: of the immunoglobulin in this cerebrospinal fluid, how much simply crossed from blood? Albumin answers the first half. It is made only in the liver, so all of it in the fluid arrived from blood, and the albumin quotient — CSF albumin over serum albumin — is a clean measurement of how permeable the barrier was at that moment. The remaining half is the hard part: given that barrier state, how much IgG should have crossed?

The Link IgG index answers it by assuming proportionality. Divide the IgG quotient by the albumin quotient, and if the ratio exceeds about 0.7 call it intrathecal synthesis. That is a straight line through the origin, and it is not what happens. Reiber’s work on cerebrospinal fluid flow describes the relationship as hyperbolic: as the barrier fails, fluid turnover slows, protein of every size accumulates, and the immunoglobulin quotients rise faster than the albumin quotient does, approaching it asymptotically. The discrimination line for each class is QLim = a·√(QAlb² + b²) − c, with the constants set by molecular size, and it is the mean plus three standard deviations of a non-inflammatory reference population — it contains 99% of people who have no intrathecal synthesis.

The practical consequence is in the first table above. Express the hyperbolic limit as the IgG index it corresponds to, and that number is not fixed: 0.62 at an albumin quotient of 2×10⁻³, 0.70 at 5×10⁻³, 0.85 at 20×10⁻³. A single index cut-off of 0.7 therefore misses real synthesis in patients with a tight barrier and invents it in patients whose barrier has failed — and a failed barrier is exactly the company that bacterial meningitis, Guillain–Barré syndrome and spinal block keep. The site’s IgG index calculator and Tourtellotte synthesis rate are still here, and should be: the index is what most laboratories report, the synthesis rate is what many neurologists were trained on, and on a sample with an albumin quotient inside its age-related limit all three methods agree. Read them together, and treat a linear index on a leaky barrier with the suspicion it deserves.

Two honest caveats belong on this page rather than in a footnote. The first is that Reiber’s superiority is no longer uncontested. Halperin and Granger, publishing in 2026 on 1,872 samples across three cohorts, point out that the hyperbolic function is very nearly linear once the albumin quotient exceeds 5×10⁻³, and that judged against oligoclonal bands as the reference standard the Reiber method discriminated worse than the plain IgG index — area under the curve 0.74 against 0.81. That is one study against three decades of European practice, and the hyperbolic model remains the standard in the laboratories that report quotient diagrams, but a reader deciding which number to believe deserves to know the argument is live. The second caveat is larger and both sides agree on it: no quotient method, hyperbolic or linear, is as sensitive as isoelectric focusing. Bands are found in roughly 95% of clinically definite multiple sclerosis, a raised IgG index in about 60%. If the question is whether there is intrathecal synthesis at all, the answer comes from the oligoclonal band pattern, and this calculation tells you how much and of which class.

Frequently asked questions

What is the Reiber quotient diagram?

A plot of the immunoglobulin quotient against the albumin quotient, with a hyperbolic reference line drawn on it. Points below the line are explained by transfer from blood; points above it indicate immunoglobulin made inside the central nervous system. Because the line curves, the diagram separates barrier dysfunction from local synthesis in a way a single ratio cannot.

How is the intrathecal fraction calculated?

IF% = (1 − QLim ÷ QIg) × 100, where QIg is the measured immunoglobulin quotient and QLim is the hyperbolic limit for that class at the patient’s albumin quotient. It expresses how much of the immunoglobulin in the fluid was produced locally. Reiber’s manual advises against calling a fraction elevated below 10%, because between-laboratory variation in the four underlying measurements is larger than that.

Why does the IgG index give a different answer?

Because it assumes the relationship between the two quotients is a straight line through the origin and it is not. Expressed as an index, the hyperbolic limit rises from about 0.62 at an albumin quotient of 2×10⁻³ to about 0.85 at 20×10⁻³. A fixed cut-off of 0.7 is therefore too strict when the barrier is tight and far too lenient when it has broken down, which is when it most often gets used.

Which immunoglobulin class should be measured?

All three where the laboratory offers them, because the dominant class is itself diagnostic information. An IgG-dominant response fits multiple sclerosis, neurosyphilis or HIV encephalitis; IgA dominance is described in neurotuberculosis, brain abscess and adrenoleukodystrophy; IgM dominance in Lyme neuroborreliosis, mumps, central nervous system lymphoma and African trypanosomiasis. Measuring IgG alone reduces the test to yes or no.

Is a normal albumin quotient needed for this calculation?

No — the opposite. The hyperbolic limit exists precisely so that the calculation stays valid when the barrier is disturbed, and it moves with the albumin quotient automatically. What the albumin quotient does is tell you whether the barrier is abnormal for the patient’s age, using QAlb(ref) < (4 + age÷15) × 10⁻³, and that is reported separately because it is a finding in its own right.

Does a negative intrathecal fraction mean something is wrong?

No. It just means the measured quotient sits below the discrimination line, which is where most samples sit. The number is the signed distance from the line, so it is negative whenever there is no intrathecal synthesis to detect. Report it as none detected rather than as a negative quantity of immunoglobulin.

Related calculators

References

Reiber H. Cerebrospinal fluid — Laboratory Analysis, Evaluation and Interpretation. 2020 edition. Available at horeiber.de.
Reiber H. Flow rate of cerebrospinal fluid (CSF) — a concept common to normal blood-CSF barrier function and to dysfunction in neurological diseases. J Neurol Sci. 1994;122(2):189–203.
Reiber H, Peter JB. Cerebrospinal fluid analysis: disease-related data patterns and evaluation programs. J Neurol Sci. 2001;184(2):101–122.
Halperin JJ, Granger D. Intrathecal antibody synthesis — Reiber method revisited. BMC Neurol. 2026;26:531.
Deisenhammer F, Zetterberg H, Fitzner B, Zettl UK. The cerebrospinal fluid in multiple sclerosis. Front Immunol. 2019;10:726.

Medical Disclaimer: The tools and content provided here are for educational and reference purposes only. They are not intended to substitute for professional medical advice, diagnosis, or treatment. Clinical decisions should always be based on the comprehensive assessment of a qualified healthcare professional.