HLA Typing — Transcript

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1. 0:02successful
2. 0:04either tissue or organ transplantation
3. 0:08that it depends
4. 0:11to a large extent on the minological
5. 0:14compatibility.
6. 0:16those coming now you're disturbing milk
7. 0:19that it depends to a large extent on the
8. 0:22minological compatibility
9. 0:24between the donor and the recipient
10. 0:28and that we also say that the human
11. 0:32immune system is designed to recognize
12. 0:36and also eliminate foreign substances.
13. 0:40So a transplanted organ can be
14. 0:43identified as foreign and attacked if
15. 0:46not if it is not properly cross matched.
16. 0:51It does not match the host the the
17. 0:54recipients. So the human luccoside
18. 0:57antigen system is central to this
19. 1:00recognition.
20. 1:01Okay. So is very very fundamental
21. 1:07and we must take note of it in dun
22. 1:10selection and transplant outcome. The
23. 1:13HLA system is very very important to
24. 1:16this recognition of tissues and organ
25. 1:20transplantations
26. 1:22and we also said earlier in our first
27. 1:24lecture that the HLA molecule is highly
28. 1:27polymorphic.
29. 1:29It has highly polymorphic
30. 1:32has highly polymorphic cell surface
31. 1:34proteins
32. 1:36that are encoded by gene within the
33. 1:38major histompatibility
34. 1:41complex chromosome 6.
35. 1:45Okay. So this lecture we are going to
36. 1:48look at um HLA typing.
37. 1:52HLA typing. When we do HLA typing, we
38. 1:55actually determining the HLA alals or
39. 2:00antigens that are expressed by the donor
40. 2:05and the recipients.
41. 2:07Okay, just like we have in our blood
42. 2:11grouping, reverse blood grouping. Okay,
43. 2:14so we are trying to when we do typing,
44. 2:18HLA typing, we are trying to determine
45. 2:21the HLA
46. 2:24We're trying to determine the
47. 2:27HLA
48. 2:30also
49. 2:36and the recipients.
50. 2:38Okay. So, and when we do this typing, we
51. 2:42talked about class one and class two. We
52. 2:45are actually looking at those class one
53. 2:49and class two where we have the for
54. 2:51class one we have the HLA A HLA B and
55. 2:55HLA C okay we're also looking out for
56. 3:00the alals in the class two where we have
57. 3:03the HLA DR the HLA DQ and the HLA DP
58. 3:10okay so this is what we are trying to
59. 3:13cross match or do
60. 3:17um we'll try to look at the techniques
61. 3:20that are involved in doing this.
62. 3:27So we also look at antibbody screening
63. 3:32antibbody screening and also the methods
64. 3:36that are used the process.
65. 3:41Okay.
66. 3:43So both blood grouping compatibility
67. 3:46compatibility and HLA typing
68. 3:49antibbody printing specific antibbody
69. 3:52assessment and cross matching. These are
70. 3:54the
71. 3:56techniques or process that will provide
72. 3:59complimementary information
73. 4:02and their combination will give us an
74. 4:05interpretation of the compatibility of
75. 4:08the cross match.
76. 4:13people that are coming in there. So in
77. 4:16the laboratories we perform HA test to
78. 4:20support
79. 4:21uh to support transplant programs. This
80. 4:25include HLA typing of recipients and
81. 4:28prospective donor
82. 4:30like I've said HLA cross matching have
83. 4:33antibbody screening and antibbody
84. 4:36identification. And as we go along we'll
85. 4:38take our analogy from our blood
86. 4:41grouping which you are very very
87. 4:43conversant with very very conversant
88. 4:47with the ABU blood grouping. So for
89. 4:52process of compatibility for HLA anti
90. 4:56have undergone
91. 4:59there's there's been a lot of um
92. 5:02advancement in the process of cross
93. 5:04matching for HLA. Okay something that
94. 5:08starts with um just like we have in our
95. 5:11blood grouping we have various
96. 5:14techniques of doing our reverse blood
97. 5:16grouping. So also it extends to HLA
98. 5:20typing and you know that in HLA typing
99. 5:23we are trying to look at the lymphocytes
100. 5:27while in blood grouping we are
101. 5:29looking at the the rest cells and the
102. 5:32antibodies to the rest cells. Yeah we're
103. 5:34looking at the lymphocytes antigens and
104. 5:38antibodies against them.
105. 5:42So the process of uh carrying out this
106. 5:46uh compatibility testing or cross
107. 5:48matching have evolved have advanced. We
108. 5:52we've started with they started with a
109. 5:55simple cerological process
110. 5:59started with simple cerological process
111. 6:01where the mechanism involved using a
112. 6:04viable donor and recipient lymphocytes.
113. 6:09Okay. They are incubated with specific
114. 6:13anti-HLA
115. 6:14sera just like we have our blood
116. 6:17grouping sera. So we're making use of
117. 6:20lymphocytes just like we use red blood
118. 6:23cells in our blood grouping. So here
119. 6:26we use viable
120. 6:29viable that is lymphocytes that are
121. 6:33viable
122. 6:35both from the donor and the recipients.
123. 6:38Then you cubate it with specific
124. 6:39anti-HLA
125. 6:41sera okay
126. 6:44which is usually uh uh from multiparus
127. 6:49women or people that have received
128. 6:51multiple blood transfusion they can
129. 6:53affect their sera to produce this ha
130. 6:56antisera and also a rabbit complement is
131. 6:59included so binding together of the
132. 7:03antibbody
133. 7:05just like we have in also blood grouping
134. 7:08will trigger complement membrane attack
135. 7:12and when compliment membrane attack
136. 7:14occurs there will be cell lis and the
137. 7:18die components of the reaction means
138. 7:20will be able to penetrate into the cell
139. 7:24the lymphocytes and we now view it under
140. 7:26the microscope. So that is to what the
141. 7:31process that cerological uh HLA typing
142. 7:35under goes cerology from the name. Okay.
143. 7:39So but its main limitation is that um
144. 7:42that of uh lack of specificity because
145. 7:45of high cross reactivity. So it's
146. 7:49actually nonspecific
147. 7:52[snorts] and lack of mono specific
148. 7:56antisera for that. Okay. So we can also
149. 7:59have a false positive and a false
150. 8:02negative result. Another process another
151. 8:07techniques that can be used for typing
152. 8:10HLA typing protocol is the molecular
153. 8:14method. This molecular method involve
154. 8:17PCR methods. PCR methods such as PCRSO
155. 8:24sequence specific oligourotide
156. 8:27uh PCR SSP,
157. 8:30PCR SBT. These are all DNA based
158. 8:34[snorts] amplification. Okay, they are
159. 8:36all DNA based
160. 8:40late. They are all DNA based
161. 8:43amplification using sequence specific
162. 8:47oligoucleotide probes and primer. Then
163. 8:50the next advancement the the next
164. 8:53development on the molecular uh
165. 8:56technique of typing for HLA antigens and
166. 9:02anti
167. 9:04for HA typing is the next generation
168. 9:08sequencing the NGS process is a
169. 9:13development on the molecular technique
170. 9:15era is another refinement of molecular
171. 9:19technique.
172. 9:20because the process is um it covers the
173. 9:24complete genome instead of taking a
174. 9:26specific you know in the molecular uh
175. 9:29technique the molecular methods of the
176. 9:31PCR there's what we call the primers and
177. 9:35the probes these are specific uh DNA
178. 9:38sequences to identify a specific target
179. 9:42on the gene okay so but the next
180. 9:45generation sequencing protocol covers it
181. 9:49it can covers a whole genomic DNA
182. 9:53region. Okay. So that is an advantage.
183. 9:57So it has an advantage of eliminating
184. 10:01uh typing ambiguities.
185. 10:03Okay. It can also detect novel als
186. 10:08because it covers the whole uh DNA
187. 10:11region of the HLA gene. You can identify
188. 10:14something novel that not been identified
189. 10:17before. can also identify the no also
190. 10:23and it's fast it's faster than the
191. 10:26ordinary PCR process.
192. 10:30So these techniques are
193. 10:32what they can apply to do HLA typing
194. 10:36especially the cerological techniques
195. 10:38which you can um
196. 10:42uh draw an analogy between that and our
197. 10:46blood groupings you can easily
198. 10:49understand that more than the um DNA
199. 10:54based techniques which
200. 10:57uh we don't have any practical um
201. 11:01aspects.
202. 11:03Excuse me, let me admit this late
203. 11:05commerce.
204. 11:07Okay.
205. 11:11So in blood group you know we
206. 11:14determine whether a person possesses A B
207. 11:18or both or neither of the antigens. So
208. 11:21similarly in HLA typing we determine the
209. 11:25HLA antigen or alles inherited by the
210. 11:29donor or recipient. So I'm just trying
211. 11:32to draw this analogy so that you can
212. 11:35liking it and you can understand them
213. 11:38what we what I'm trying to say faster.
214. 11:42Okay.
215. 11:48So,
216. 11:54so these are the techniques we can use.
217. 11:58So, we also have a cross matching
218. 12:01process. If you draw that analogy in red
219. 12:05cell cross match, you know, you get the
220. 12:08recipient plasma.
221. 12:11Okay. And the donor red cell. So in HLA
222. 12:15cross match you get the recipient serum
223. 12:20and donor lymphocytes
224. 12:22or other donor cells you're trying to
225. 12:24cross match. So the red cell and then
226. 12:28the lymphocytes. Okay.
227. 12:32Okay. So there are some uh the cross
228. 12:35matching process we have the
229. 12:37sensization. This is a panel reactive
230. 12:40anti- antibbody. Panel reactive
231. 12:43antibbody. We are trying to screen the
232. 12:47um we are trying to screen the patient
233. 12:51to know the percentage of his uh
234. 12:57lymphocy percentage antibbody antibbody
235. 13:00reactivity to determine whether you'll
236. 13:02be able to get a donor
237. 13:06for the patient. So it measures patient
238. 13:09sensitization against a panel of 100
239. 13:13donor antigen. The clinical implication
240. 13:16is that assuming you did P R A you carry
241. 13:22that P that 80%
242. 13:25there's an 80% uh um positivity it means
243. 13:31that the patient is fundamentally
244. 13:34incompatible
245. 13:35with 80% of the donor population. Okay.
246. 13:41it has been the patients have been
247. 13:43sensitized much. So that if you look for
248. 13:47a donor for that patient in that
249. 13:49population because the P
250. 13:54is high you may not be able to get a
251. 13:57donor for the patient.
252. 14:02Okay. Also, they can also carry out uh a
253. 14:06visual cross match which predicts
254. 14:08compatibility by comparing the
255. 14:11recipients precise antibbody profile
256. 14:15against a prospective donor's high
257. 14:18resolution HLA typing bypassing physical
258. 14:22testing delays. So, this is trying to
259. 14:26match the patient profile against
260. 14:29already established profile. Okay, that
261. 14:33will also give you a clue to how
262. 14:38uh whether there will be available how
263. 14:40easy or how easy you can assess a donor
264. 14:44for this patient in this population
265. 14:46either the P or the visual cross match.
266. 14:52These are the processes that are
267. 14:54involved in HLA compatibility testing.
268. 14:58Now we have also the physical cross
269. 15:01matching.
270. 15:04Say this commas.
271. 15:08We have also um the physical cross
272. 15:12matching where we do a antibbody
273. 15:16uh screening antibbody screening
274. 15:20using the
275. 15:23uh CDC process implement dependent
276. 15:27cytoxicity.
277. 15:30Okay. So here the the donor is the
278. 15:35traditional baseline. You're going
279. 15:37you're just like in our cerological
280. 15:39testing you're trying to uh establish
281. 15:43the traditional baseline then detect
282. 15:46complement fixing IGG and IGM.
283. 15:52Okay. Here the donor lymphocytes the
284. 15:55donal lymphocytes and the recipient
285. 15:57serum plus the compliment. Okay. are
286. 16:01incubated together and scored by
287. 16:04percentage of dead cell. Okay. So when
288. 16:07you incubate the donal lymphocytes plus
289. 16:11the recipient serum and the compliments
290. 16:14that are added. Okay.
291. 16:18After the incubation observe the cells
292. 16:23under the microscope. Okay. So by using
293. 16:26the dye. Okay. so that you'll be able to
294. 16:29identify percentage of dead cells.
295. 16:36So the disadvantage include inability to
296. 16:39detect low teta antibodies
297. 16:44is inability to detect low ta
298. 16:47antibodies. We have another pro uh
299. 16:51process we can also do cross ha cross
300. 16:54matching which is the
301. 16:57flowcytometric
302. 16:58flow cytotric uh cross match. It uses
303. 17:04fluorescent label antibodies.
304. 17:07Okay.
305. 17:09like three colors, flowcytometry
306. 17:12combining donol lymphocytes,
307. 17:14recipient serum, fluoroc antihuman IGG
308. 17:20along with the markers.
309. 17:23Okay, it is highly sensitive for
310. 17:26detecting non complement fixing.
311. 17:33So the flowcytometric method is highly
312. 17:37sensitive for detecting
313. 17:41non
314. 17:43complement
315. 17:45fixing or low ta donor specific
316. 17:50antibodies.
317. 17:52So those antibodies
318. 17:54that cannot fix the compliment
319. 17:58using flowcytometric cross match method
320. 18:01in HA uh cross matching can identify
321. 18:06those antibodies.
322. 18:09We also have the uh solid phase
323. 18:13uh luminex cross match based assay. So
324. 18:18it's a it's it's a micro bead assay
325. 18:21utilizing donor cell donor cell lysate
326. 18:28that utilizes donor cell lysate bound to
327. 18:32monoconal antibodies
328. 18:34monoconal antibbody coated bits. It also
329. 18:38detects donor specific antigens
330. 18:41without requiring intact donor cell. So
331. 18:45each of these cross matching process
332. 18:48have their uh advantage and uh have
333. 18:51their um advantage each of them have an
334. 18:55advantage over the it has over the
335. 18:58other. Okay. While the fluorescent um
336. 19:03the flow the flowcytotric uh crossmatch
337. 19:06process helps us to identify
338. 19:10non-complent fixing or low ta dun
339. 19:14specific antibodies. The um solid phase
340. 19:18luminous crossmatch u platform helps us
341. 19:23to detect antibodies without require
342. 19:27that may not require intact donor cells.
343. 19:30So you can see the advantage of each
344. 19:33over the other. These are process of HLA
345. 19:37cross matching.
346. 19:44So we also have um
347. 19:49uh I've talked about antibbody screening
348. 19:52talked about HLA cross matching. So
349. 19:54we're going to discuss briefly on um the
350. 19:58clinical applications
351. 20:01of HLA in transfusion medicine which is
352. 20:05what we have discussed if you go back to
353. 20:10our yes complications of blood
354. 20:14transfusion.
355. 20:16This is where it sits also. So, so I
356. 20:20refer you back to our lecture in your
357. 20:23fourth year where we did complications
358. 20:26of blood
359. 20:29transfusion.
360. 20:31Okay. So here in the uh process of organ
361. 20:37transplantation organ clinical
362. 20:39implication of the HLA complex in solid
363. 20:43organ and stem cell transplantations.
364. 20:48Okay. solid organs. When we talk about
365. 20:50solid organs, we talk about the renal
366. 20:53transplantation.
367. 20:55Classic example.
368. 20:57So lina renal transplantation we know
369. 21:00requires
370. 21:02matching the HLA class one and class 2.
371. 21:07Okay. Especially HLA A, HLA B, HLA DR.
372. 21:13Okay.
373. 21:15So renal transplantation requires
374. 21:19matching the HLA complex of both the
375. 21:23donor and the recipients.
376. 21:27Okay.
377. 21:29So uh to prevent what we term as
378. 21:35graft rejection.
379. 21:39Okay. And graph rejection can be direct.
380. 21:43When it is direct,
381. 21:45we call it can also be referred to as
382. 21:48acute
383. 21:49acute rejection of the graft that is
384. 21:53being transplanted to the recipient or
385. 21:56it can be uh chronic rejection that is
386. 22:01the mechanism of initiating it may be
387. 22:03indirect alo recognition.
388. 22:07So in the direct alo recognition or
389. 22:12acute rejection of transplanted tissue
390. 22:17the mechanisms there is that the donor
391. 22:20APC cells the donor antigen presenting
392. 22:25cells
393. 22:27presents donor peptides
394. 22:31directly to recipient T- cell. That is
395. 22:35what will drive the acute rejection.
396. 22:42Excuse me.
397. 22:43The donor APC cells
398. 22:47presenting donor peptides. So these are
399. 22:50already performed.
400. 22:52Okay. These are already performed in the
401. 22:55donor that at the point of
402. 22:59transplantation
403. 23:02this donor APC cell presents this
404. 23:05antigens immediately directly to the
405. 23:08recipient's T- cells and once that is
406. 23:12done it initiates
407. 23:15uh reactions tissue reactions
408. 23:18drives the acute rejection. Okay, it
409. 23:21initiates reactions. Okay, and once that
410. 23:25happens, what happen is that um a
411. 23:28trombus may be formed at that point of
412. 23:32um uh engraftment.
413. 23:36Okay. And once a trombus is formed, you
414. 23:38know, trombosis, it to prevent block
415. 23:42blood flow into the transplanted organs.
416. 23:47And once that happens, the blood supply,
417. 23:50as I told us earlier, the blood supply
418. 23:54is cut off. The blood supply is cut off.
419. 23:57Nutrients is the blood that carries the
420. 23:59nutrients. The blood that carries the
421. 24:02oxygen. All this oxygen, nutrient supply
422. 24:06to the transplanted organ is cut off and
423. 24:10the transplanted tissue dies off.
424. 24:15So that is the mechanism of this uh
425. 24:18rejection we are talking about so that
426. 24:22the engraftment does not uh fit to the
427. 24:26recipient. So it can be direct aloe
428. 24:30recognition just like I've told us the
429. 24:34donor APC cell presenting donor peptides
430. 24:37performed already directly to the
431. 24:40recipient T cells or it can happen in an
432. 24:44indirect alo recognition
433. 24:46uh process which we call the um uh
434. 24:50chronic rejection. So here the recipient
435. 24:54we are not talking we we are now talking
436. 24:57about the recipient APC cells. The
437. 25:00direct arrow recognition has to do with
438. 25:02the donor APC cells already
439. 25:07having peptides
440. 25:09processed already and presenting it
441. 25:11immediately to the recipient. While in
442. 25:14the indirect arrow recognition, we are
443. 25:16talking about that the the recipients
444. 25:19APC
445. 25:21cells antigen processing cells process
446. 25:24shared donor antigens. Okay,
447. 25:29some
448. 25:31donor antigens that it could not
449. 25:33recognize at cells, it will process it
450. 25:36and then present them to the recipient's
451. 25:41tea cells. So the recipient recognizing
452. 25:44some dead donor antigen as nonself
453. 25:48processing it and presenting it to its
454. 25:51own T- cell. Okay, that will drive the
455. 25:54chronic uh rejection. We also have the
456. 25:58hyperacute
457. 26:00rejection. This is mediated by um
458. 26:05preformed or anti-HLA antibodies
459. 26:09that already preformed causing
460. 26:11compliment activation and vascular
461. 26:14endotellia damage trombosis and rapid
462. 26:17graft loss. So you need to be able to
463. 26:22understand the mechanism of each of
464. 26:24these um uh organ trans rejection
465. 26:28mechanism both the direct aloe
466. 26:30recognition the indirect aloe
467. 26:32recognition causing chronic rejection
468. 26:35and the hyperacute rejection that are
469. 26:38mediated by preformed and anti-HLA
470. 26:43antibodies
471. 26:46okay that will now cause immediately
472. 26:49compliment ment fixation, vascular
473. 26:51endothelial damage, uh trombosis and
474. 26:56eventually
475. 26:58graft loss, rejection and loss.
476. 27:03Okay, so these are some of the clinical
477. 27:06significance
478. 27:08of HLA
479. 27:10uh complex in solid organ
480. 27:13transplantation.
481. 27:15It also um has the significance in
482. 27:19hemopetic
483. 27:21hematopoetic stem cell transplants in
484. 27:25hematopoetic
485. 27:28stem cell transplantation.
486. 27:32Okay. So the also the hematopoetic cell
487. 27:36transplantation
488. 27:38requires strict alo
489. 27:43matching
490. 27:51matching 100%. Okay. Any incompatibility
491. 27:56will risk graph failure immediately or
492. 27:59can result in life threatening graph
493. 28:04versus host disease.
494. 28:08Again
495. 28:09remember your 422
496. 28:12where we talked about complications of
497. 28:15blood donation where we explain that
498. 28:19because the lymphocytes cross match are
499. 28:23not being carried out during uh red
500. 28:27blood cell transfusion. They still poses
501. 28:30some risk in blood transfusion. The same
502. 28:34process is applicable in this HLA
503. 28:38transplantation
504. 28:40where we don't where we are trying to
505. 28:43cross match but probably the cross match
506. 28:45is not 100%.
507. 28:47So so any incompatibility can risk graph
508. 28:51failure or can lead to lifethreatening
509. 28:55graph versus host disease.
510. 29:03versus host disease. We also explained
511. 29:05it that the donor T- cell attack
512. 29:09recipient what tissue.
513. 29:14So we've said that you can refer
514. 29:16yourself back to the
515. 29:20uh the notes that's what this diagram is
516. 29:23trying to also um depict.
517. 29:27So we also have the HLA complex also a
518. 29:31significant role in transition medicine.
519. 29:36We've said that aloe immunization of
520. 29:40platelets.
521. 29:42Okay. I've also explained that where
522. 29:46some persons lack the platelets antigen.
523. 29:51Okay. Multiple
524. 29:54random transfusion.
525. 29:56Okay. Where some persons lack the
526. 29:58platelet antigen but when they get
527. 30:01transfused with this uh blood know blood
528. 30:05also contains some uh uh platelets
529. 30:09especially when we don't practice
530. 30:11component
531. 30:13component
532. 30:15separation of blood into their different
533. 30:17separation of blood into their different
534. 30:19components especially where we transfuse
535. 30:22whole blood we are saying some that some
536. 30:25persons
537. 30:26lack the common platelet antigen and
538. 30:30when they get transfused the their
539. 30:33platelets develop HLA patient develop
540. 30:36HLA class one aloe antibodies destroying
541. 30:39donor platelets
542. 30:42okay which will lead to platelet
543. 30:46refractoryiness
544. 30:48a process where the expected increase
545. 30:52expected increase does not happen even
546. 30:55after transfusion of platelets even
547. 30:57after transfusion because the platelets
548. 31:00are being destroyed. Okay. Also um in
549. 31:07transfusion medicine the HLA complex can
550. 31:10also be implicated in fibr non-hemolytic
551. 31:15transfusion reaction. Okay. In fibr
552. 31:19non-hemolytic transfusion reaction where
553. 31:23the temperature rises up to 1% driven by
554. 31:26recipient HLA or granuloite antibod is
555. 31:31reacting against donor component all
556. 31:34again because we do not cross match for
557. 31:39the uh HLA complex antigens
558. 31:44or granulosytes antibodies we don't do
559. 31:47that cross matching on normal blood
560. 31:49transfusion. So they still posess some
561. 31:52reactions even when the red blood cell
562. 31:56compatibility
563. 31:57is um good. So the lymphocytes the white
564. 32:01cell poses their own problem which can
565. 32:04be in form of the fibr nolytic
566. 32:08transfusion reaction.
567. 32:13So another complications which can
568. 32:16result as a result of incompatibility
569. 32:19from the HLA complex in is um severe
570. 32:23complications can be tr okay and
571. 32:27transmission associated graph vessels
572. 32:30host disease which you also discussed in
573. 32:34details. You can see I just try to
574. 32:36summarize it here because we have dealt
575. 32:39with it in 421 excessively. So you can
576. 32:42go back to your 421 and read the
577. 32:44detailed description of PRI and
578. 32:49C A G VHD. So the mechanism again is
579. 32:54that antibodies in donor plasma
580. 32:57against HLA class one or class 2 or
581. 33:00neutrofils attack recipient
582. 33:04cells. Okay, see that's happening at the
583. 33:08lung. The complement activation when
584. 33:10they attack the cells that is complement
585. 33:12activation neutrofil sequestration in
586. 33:16the lungs leading to acute
587. 33:18non-cardiogenic
588. 33:19pulmonary edema
589. 33:23in transmission associated graph versus
590. 33:25host disease the mechanism is that the
591. 33:28donor lymphocy engraft
592. 33:30in a susceptible recipient and mount an
593. 33:35immune attack.
594. 33:38Okay, we can prevent that
595. 33:41by gamma radiation or cellular blood
596. 33:44product
597. 33:46uh to inactivate donor lymphocytes. So
598. 33:49these are some of the complications of
599. 33:52the HLA complex in blood transfusion
600. 33:56transfusion medicine.
601. 34:03Right?
602. 34:05So the HLA complex is also um
603. 34:11uh the HLA complex can be also be
604. 34:14associated
605. 34:16with some diseases.
606. 34:18Take for example the HLA
607. 34:22B27
608. 34:24that is strongly associated with anosin
609. 34:28spondilitis.
610. 34:30Okay.
611. 34:31It's
612. 34:33more prevalent in AS patients. Okay. And
613. 34:38other spong
614. 34:40other
615. 34:42um HLA antigens too. Um
616. 34:47okay. You can see this um HLA Dure 2 is
617. 34:52a major genetic risk factor for celiac
618. 34:55disease. So some of the HLA um antigens
619. 34:59um associate with some diseases.
620. 35:04Okay.
621. 35:08So the HLA is the ultimate molecular ID
622. 35:14driving self tolerance and adaptive
623. 35:17immunity.
624. 35:19Say that in our first lecture.
625. 35:22Okay. because he tries to identify
626. 35:26nonself and tries to eliminate that.
627. 35:30Okay. So transitioning from cerology
628. 35:34to NGS
629. 35:36and visual cross matching has re
630. 35:39revolutionalize
631. 35:41matching accuracy
632. 35:43and also mastering the HLA typing
633. 35:48directly detects outcome in
634. 35:50transplantation and also prevents fetal
635. 35:53transfusion reactions.
636. 35:56Okay. So
637. 35:59that is the HLA system. I don't know if
638. 36:02any of you have any question. I try to
639. 36:06summarize it because the bulk of it is
640. 36:08our complications of transmission
641. 36:11reaction. So I don't want to extend that
642. 36:14to okay. So you can ask your question