High sensitivity method for early Lyme disease detection
The present disclosure provides methods for detecting early Lyme disease. The present disclosure provides a biosignature indicative of the presence or absence of Borrelia burgdorferi infection.
1. A method of diagnosing and treating early Lyme disease in a subject in need thereof, the method comprising:
diagnosing the subject with early Lyme disease when a set of abundance values comprising an abundance value for each of at least forty-four molecular features in a test biological sample from the subject is indicative of Lyme disease in the subject, wherein the abundance values are obtained by subjecting the sample to a high resolution mass spectrometry (MS) analysis and the at least forty-four molecular features comprise:
Molecular
Retention
Feature No.
Mass
Time
1
327.241
17.2749
2
697.7808
16.311
3
1119.6309
18.0691
4
285.1371
17.1739
5
895.6035
17.1609
6
566.3622
18.7675
7
314.2455
19.1192
8
428.3643
19.7699
9
594.5294
18.7519
10
463.1829
16.4529
11
978.7187
17.4282
12
1298.7255
18.3314
13
779.5233
16.9309
14
1305.8809
18.7568
15
806.7469
18.7066
16
530.2133
17.6981
17
356.2203
17.2324
18
430.2573
17.4122
19
324.2412
17.8765
20
794.5341
17.8858
21
307.2876
18.6806
22
427.3653
17.91
23
334.2142
17.3512
24
351.1585
15.9086
25
471.339
17.0609
26
792.4026
16.4326
27
1430.8031
18.3137
28
467.2999
17.95
29
496.3583
17.4884
30
728.4819
17.8244
31
238.0845
16.2331
32
584.2643
16.8327
33
278.2242
17.869
34
285.1934
16.2458
35
614.49
19.7423
36
358.2457
17.2135
37
810.4975
17.2056
38
680.466
19.9867
39
2108.9954
16.0506
40
658.3397
16.1767
41
672.1464
16.2089
42
871.5718
19.9449
43
329.2392
17.5061
44
661.3387
15.9866;
and
administering an amount of at least one antibiotic effective for the treatment of early Lyme disease to the diagnosed subject, wherein the cumulative amount of the at least one antibiotic effective for the treatment of early Lyme disease is less than the cumulative amount of the antibiotic effective for the treatment of late stage Lyme disease.
2. The method of claim 1 , wherein the abundance values further comprise an abundance value for any one or more of the molecular features selected from:
Molecular
Retention
Feature No.
Mass
Time
45
1324.5212
16.2149
46
296.1625
17.6643
47
645.4677
17.4282
48
1388.9319
17.6689
49
517.3853
18.0033
50
700.4406
18.0264
51
805.5735
17.6313
52
428.3654
20.0453
53
548.3212
16.7219
54
550.4561
19.1554
55
592.4701
19.0466
56
601.4389
17.4515
57
610.4214
19.0052
58
882.5909
18.2339
59
926.6162
18.2273
60
679.4172
16.7353
61
431.3026
17.643
62
1551.059
18.7359
63
1068.7148
18.4538
64
312.1471
15.9215
65
1259.4886
15.7325
66
136.0388
1.498
67
158.0206
1.4863
68
386.276
17.8173
69
860.6066
18.234
70
921.6618
18.2278
71
254.1159
17.0932
72
1358.9095
17.7304
73
296.236
19.0046
74
979.05
17.4291
75
647.4071
16.6695
76
303.2562
18.3335
77
344.2206
17.408
78
284.2141
17.9876
79
303.2537
18.5589
80
336.233
17.4137
81
358.2142
17.3947
82
278.2243
18.4237
83
294.2199
17.8142
84
342.2406
17.3501
85
305.272
18.4624
86
1396.5468
16.3162
87
260.2143
18.1301
88
325.2257
17.2256
89
242.1265
15.2659
90
332.1984
17.1576
91
332.1986
17.1585
92
1995.0544
16.1758
93
1425.9312
17.9419
94
1026.0385
15.8432
95
329.2567
17.7914.
3. The method of claim 1 , wherein the at least one antibiotic is amoxicillin, doxycycline, cefuroxime axetil, amoxicillin-clavulanic acid, macrolides, ceftriaxone, cefotaxmine, penicillin G, or combinations thereof.
4. The method of claim 1 , wherein the high resolution mass spectrometry system comprises a liquid chromatography-mass spectrometry (LC-MS) system.
5. The method of claim 1 , wherein the abundance value for each molecular feature is obtained from a measurement of the area under the peak for the monoisotopic mass of each molecular feature.
6. The method of claim 1 , wherein the method correctly distinguishes the subject with early Lyme disease from a subject without Lyme disease, with a specificity of at least 90%.
7. The method of claim 1 , wherein the method correctly identifies at least 77% of subjects with early Lyme disease, wherein the subjects are serology negative for Lyme disease.
8. The method of claim 1 , wherein the set of abundance values of the test biological sample are determined to be indicative of Lyme disease by determining the relative abundance of each molecular feature in the biological sample with respect to a control biological sample from a control subject.
9. The method of claim 8 , wherein the control subject is selected from a healthy subject, a subject suffering from a disease with overlapping symptoms, a subject exhibiting serologic cross-reactivity with Lyme disease, and a subject suffering for another spirochetal infection.
10. The method of claim 9 , wherein the disease with overlapping symptoms is selected from syphilis and fibromyalgia.
11. The method of claim 9 , wherein the serologic cross-reactivity is due to a disease selected from infectious mononucleosis and syphilis.
12. The method of claim 9 , wherein the other spirochetal infection is selected from syphilis and severe periodontitis.
13. The method of claim 1 , wherein the set of abundance values of the test biological sample are indicative of Lyme disease when the abundance value of molecular feature 1, 3, 5, 8, 13, 15, 17, 18, 19, 20, 21, 23, 30, 31, 33, 35, 36, 37, 39, 40, 41, 42, 43, and 33 is increased relative to the abundance value in a control biological sample.
14. The method of claim 1 , wherein the abundance values of the test biological sample are indicative of Lyme disease when the abundance value of molecular feature 2, 4, 6, 7, 9, 10, 11, 12, 14, 16, 22, 24, 25, 26, 27, 28, 29, 32, 34, and 38 is decreased relative to the abundance value in a control biological sample.
15. The method of claim 1 , wherein the abundance values of the test biological sample are indicative of Lyme disease when the abundance value of molecular feature 1, 3, 5, 8, 13, 15, 17, 18, 19, 20, 21, 23, 30, 31, 33, 35, 36, 37, 39, 40, 41, 42, 43, and 33 is increased relative to the abundance value in a control biological sample and the abundance value of molecular feature 2, 4, 6, 7, 9, 10, 11, 12, 14, 16, 22, 24, 25, 26, 27, 28, 29, 32, 34, and 38 is decreased relative to the abundance value of the molecular feature in the control biological sample.
16. The method of claim 1 , wherein the test biological sample is a serum sample.
17. The method of claim 1 , wherein the Lyme disease is caused by an infection of a Borrelia species that causes Lyme disease.
18. The method of claim 17 , wherein the Borrelia species is Borrelia burgdorferi.