Significant correlation between serum DOTL1 levels and pain intensity, sensitivity, and psychological distress in women with fibromyalgia,2025, Erdem+

Significant correlation between serum DOTL1 levels and pain intensity, sensitivity, and psychological distress in women with fibromyalgia

Erdem, Mehmet; Kiran, Tuğba Raika; Otlu, Önder; Aydoğan Baykara, Rabia; İnceoğlu, Feyza

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Disruptor of telomeric silencing 1-like (DOT1L) is a protein involved in epigenetic regulation, as well as in the Wnt and hypoxia signaling pathways. DOT1L has been found to play a role in the pathogenesis of various diseases associated with these pathways. In this study, it was aimed to determine serum DOT1L levels in patients with fibromyalgia (FM) and its association with disease activity.

Forty-eight patients diagnosed with FM according to the 2016 American College of Rheumatology criteria and 48 healthy controls were included in the study. Disease activity was measured using clinical questionnaires (Fibromyalgia Impact Questionnaire [FIQ], Visual Analog Scale [VAS], Widespread Pain Index [WPI], Symptom Severity Score [SSS], Pittsburgh Sleep Quality Index [PSQI], Fatigue Severity Scale [FSS], Hospital Anxiety Scale [HAS] and Hospital Depression Scale [HDS]) and DOT1L levels were assessed using Enzyme-Linked ImmunoSorbent Assay in all serum samples. Additionally, routine biochemical analyses were performed.

Pain duration, FIQ, VAS, WPI, SSS, PSQI, FSS, HAS, and HDS were found to be statistically significant higher in FM compared to the control group (P = .001). Compared with the control group (0.53 ± 0.12 ng/mL), DOT1L concentrations were significantly higher in patients with FM (1.47 ± 0.13 ng/mL; P = .001). In the FM group, DOT1L levels also showed a positive correlation with the results of the all the clinical questionnaires (P = .001).

It was found that the DOT1L measurement value has a statistically significant effect in predicting the difference between the FM and control groups (P = .022). When the cutoff value for DOT1L was set at 0.315 ng/mL, it was found to have 79% sensitivity and 71.7% specificity in detecting FM.

This study highlights the potential of DOT1L as a valuable biomarker for FM diagnosis.

Link | PDF (Medicine) [Open Access]

 

If we round those measurements to 80 and 70 %, and assume a prevalence of 5 % for fibro (probably too high of an estimate), we would get the following result if we ran the test on 1,000 random people:

• 665 healthy people correctly classified as healthy
• 10 pwFibro falesly classified as healthy
• 285 healthy people falsely classified as fibro
• 40 pwFibro correctly classified as fibro

So only 12.3 % (40/325) of the people classified as fibro would actually have fibro.

 

This might be important. DOT1L seems to push signalling to interferons and maybe TGFbeta rather than TNF alpha. I am currently interested in that slant.

 

The prevalence of fibromyalgia worth the name improbably more like 0.5% so the situation is worse, but the same applies to the rheumatoid factor test - which, in the hands of a competent physician, is a useful test now that we have treatments related to rheumatoidfactora biology.

The sensitivity and specificity levels are not really that important. If DOT1L is relevant to mechanism it will be very useful.

 

How would a competent physician deal with the possibility of false positives?

 

Well, for a start, if the patient is normal and healthy without any pain then the test is unlikely to be providing information about the pain they don't have!!

 

Sure, but what if they have pain, but not fibro? Could this test possibly lead to them no exploring alternative causes for the pain if it’s positive?

I don’t think we know of this is just a marker for pain or if can differentiate based on the cause of the pain.

 

That would be a much smaller group to handle.
Test like this very often lead to bad judgments, yes, but all medicine is doneonthe basis of probabilities and these sorts of figures are as helpful any. When sensitivity and specificity get up to 98% you know that you already knew the answer before you did the test!