A. Phagocytophilum IgM Titer

Anaplasmosis often starts with fever, headache and aching muscles after time outdoors. You may never notice the tick bite. The infection can become serious, especially if you're older or have a weakened immune system, but an Anaplasma IgM result is an unreliable way to establish its cause. CDC advises against relying on IgM results alone to diagnose anaplasmosis, because IgM is less specific than IgG and can stay detectable long after an infection.

This test detects your immune response to Anaplasma phagocytophilum. A positive result can occur without active infection, and an early negative can occur while you're sick. PCR detects bacterial DNA in whole blood. It and paired IgG antibody testing have better-established roles in diagnosis. IgG is a separate class of antibody.

What the Result Measures

Anaplasma phagocytophilum lives and multiplies inside neutrophils. These white blood cells help fight infection. In North America, blacklegged ticks transmit the bacterium and can also transmit the infections that cause Lyme disease and babesiosis.

Immunoglobulin M is one class of antibody and is usually shortened to IgM. This test measures IgM reactivity in serum by indirect immunofluorescence (IFA). Serum is the liquid left after blood clots. The laboratory dilutes it in steps and places it on slides containing bacterial material. A fluorescent reagent makes IgM that binds to that material visible under a microscope.

The titer is the highest dilution at which that reaction remains visible. A result that remains reactive after more dilution indicates stronger antibody reactivity in this assay. The titer estimates antibody reactivity without providing an exact concentration or measuring the amount of bacteria in your body.

Human Granulocytic Anaplasmosis

Human granulocytic anaplasmosis is often shortened to HGA. Fever, chills, headache and muscle aches are common. Low white blood cell counts, low platelets and raised liver enzymes can add to the suspicion, but you don't need all three abnormalities to have the infection.

In a review of 465 people with PCR-confirmed anaplasmosis, only about a quarter had all three laboratory abnormalities together. Older age, other chronic illnesses, immune suppression and altered mental status were associated with hospitalization. The absence of the full laboratory pattern should not dismiss a compatible illness.

Other tick-borne infections can produce overlapping symptoms, and some occur together. Babesiosis infects red blood cells and can accompany anaplasmosis after exposure to the same tick species. A positive Anaplasma antibody result doesn't exclude another cause of fever.

Why IgM Doesn't Reliably Date the Infection

IgM is often described as an early antibody, but that description doesn't make it a dependable early test for anaplasmosis. Antibodies may be absent when symptoms begin, and IgM can remain detectable after recovery. Studies that measured IgG or several antibody classes together cannot establish the performance of this IgM-only test.

The late IgM peak in the Korean study occurred after treatment and clinical recovery. Only two people had follow-up beyond six months, so the study cannot establish when everyone's antibodies disappear. Its results show why a rising IgM result after treatment need not mean the infection is getting worse.

Antibody Reactivity in People Who Feel Well

A review of 56 studies found a pooled antibody-positive proportion of about 8%, with wide differences between populations and laboratory methods. It combined different antibody tests and wasn't an estimate of current infection or of IgM positivity in the general population.

The distinction matters in individual surveys too. About 16% of healthy adults in a western Norway study had serum IgG antibodies, which are a different antibody class from this test. In a New York blood-donor study, about 11% reacted on a non-IgM-specific immunofluorescence test, but only about a third of those reactive samples showed the study's confirmatory immunoblot pattern.

A study of roughly 10,000 US military personnel also found that the result depended on the assay: about 3% reacted on an initial antibody screen, compared with about 0.1% on subsequent immunoblot testing. Those methods differ from this IgM IFA. These findings illustrate background antibody reactivity and disagreement between assays; they do not give a false-positive rate for your result.

When Results Can Be Misleading

• Early illness: the immune response may still be developing. An absent IgM response cannot exclude anaplasmosis.
• Antibodies after recovery: IgM can persist after the illness has resolved. Longer-lasting IgG responses are better documented and can remain detectable for years; those IgG findings should not be used to assign a duration to IgM.
• Related infections: antibodies against Ehrlichia can react in Anaplasma assays. Positive results for both organisms don't establish that you have both infections.
• Other tick-borne infections: in a small study of neoehrlichiosis, four of 18 people had Anaplasma IgM or IgG reactivity despite no detectable Anaplasma DNA. The study used serum or plasma and counted either antibody class. Previous exposure and cross-reaction were possible explanations.
• Nonspecific antibody binding: rheumatoid factor is an antibody that binds to other antibodies. It can interfere with IgM assays. Sample preparation can reduce this interference, but a reactive result still needs clinical context.
• Method differences: the bacterial material on the slide and interpretation of fluorescence can affect a titer. Small Japanese studies found different IgM and IgG reactions when the bacteria used for the slides were grown in different cell types. A change between laboratories may partly reflect the assay.